Okay, I really need to start reading TFAs and stop posting during the hours when I should already be asleep.
So as some have pointed out, there was no contract between Monsanto and the farmer in question. So this does go back to an IP infringement case, contrary to my previous post. However, I do stand by my previous statements regarding the need for refuge areas, and the need to monitor GM crops to ensure they are in compliance with refuge requirements. Consequently, the farmer in question is potentially dealing a regulated crop while flouting the associated regulations. But then again, I'm not privy to every detail of the case, and may as well be talking out of my ass.
As I understand it, the issue with the replanted/cleaned seeds is a matter of intentional breach of contract rather than one of patent infringement. When you purchase their seeds, you purchase a license with them that prohibits the replanting/cleaning of the seeds. So whether or not IP was infringed is essentially irrelevant to the stipulations of the contract itself.
There's also a practical reason behind preventing the cleaning and replanting of seed. Since these seeds contain a pesticide (Bt derivative), a necessary step to maintaining the efficacy of the pesticide is planting a refuge (non-GM section) as part of the crop. If the whole crop expressed the pesticide genes, we could expect resistance to develop very quickly, but by adding in refuge areas the selective pressure decreases. The size of the refuge varies depending on the mix of proteins being expressed, and is determined by the EPA. These non-GM refuge seeds are sometimes mixed in with the GM ones at specific ratios. By cleaning/replanting the seeds, the ratio of GM to non-GM seeds changes, and the size of the refuge is no longer controlled. This creates a situation similar to the over-prescription of antibiotics that we're all familiar with; resistant pest strains will appear much more frequently. So there are reasons other than simple greed behind these contracts.
Disclaimer: I'm currently employed at Monsanto, but contracted through a third party. I am not authorized to speak on behalf of the company, and my comments should not be interpreted as such.
Since there seems to be a bit of confusion here, allow me to explain (inadequately I'm sure) why different manufacturing processes for biologics result in non-identical molecules even though the DNA sequence and folding of the amino acids is the same.
One of the primary differences is in the glycosylation of the protein. This is where sugar groups of various structures are attached to the outside of the protein and act as a sort of label to the body (distinguishing self from non-self proteins), and even within the cell itself (identifying where the protein should be placed inside of the cell). Different organisms each have their own system for attaching and interpreting these sugar groups. For instance, typical yeast Saccharomyces cerevisiae has a glycosylation profile that will cause the human immune system to attack it eventually - which will make you have an adverse reaction not only to the drug that you're taking, but any other drug produced in the same organism. The yeast Pichia pastoris has a glycosylation profile that is superficially similar to a human one, making it less likely to cause an adverse reaction, but the organism is locked down by patents. Furthermore, there's some evidence that the glycosylation is affected by the health of the cells in the culture, and the media that you're culturing them in. Frequently we'll just coat the proteins in polyethylene glycol and hope for the best.
The other place that variation occurs is in the purification processes that are used to separate the drug molecules from everything else. Many of the purification processes will alter the glycosylation profile or the folding of the protein. They're also generally rather lossy, in that the purer the protein you want, the less of it you'll end up with, and the more it will cost. We used to attach tags to the proteins so that they were easier to purify (his6 was a common one), but then there were concerns that the tag itself would become the target for an immune reaction (which, like the glycosylation, would make a person resistant to not only the drug they were taking, but any other drug that used the same tag), so the practice has been mostly discontinued.
The simple fact is that biologics will always result in mixed batches of molecules, and different manufacturing processes do directly affect that mix. The trick for biosilmilars will be to ensure that their mix is functionally similar enough to the original one; which will likely require clinical trials - meaning that cost savings won't be nearly so drastic as it is with small molecule drugs. While we've figured out how to make DNA translate to a protein of our choosing, we're not nearly as knowledgeable about how to manipulate sugar groups in a similar manner. Progress is being made for sure, but we're not there yet.
There's a company called Argos therapeutics http://www.argostherapeutics.com/ which uses proteins harvested from cancer biopsies to do the same thing. Last I checked, they were in phase 2 clinicals (efficacy testing). This is as close to personalized medicine as anyone is really able to do right now. Disclaimer: the only tie to the company that I have is that I interviewed there a couple years ago (didn't get the job unfortunately).
As I understand it, the typical American has more debt than they do fungible assets. Inflation only means that they'll have less relative debt burdening them. Of course, there's a multitude of other less desirable consequences of hyperinflation, but I'm sure a competent marketing company could make the public welcome such changes.
Disclaimer: I'm not an Economist; not even one of the armchair variety.
I'll admit, it's technically not zero coverage. But assuming something rather severe happened to my health, I'm still faced with the choice to either A: die. or B: bankrupt both myself and my immediate family (as well as possibly my extended family) for the foreseeable future. Honestly, I'm not a cruel enough person to choose B. I know there are instances where the costs get covered, and I do personally know people that have had that happen, but I also personally know people who have been forced to sell their houses over medical debts of relatives.
Personally, I'm still rather irritated that a significant portion of my taxes went towards 'health care', and yet I still have zero coverage. I realize that this particular discussion has been beaten to death around here, so don't feel like you have to reply. I just want to complain about it somewhere.
In a lot of cases, I'd agree with you. Unfortunately, the release schedule stateside is fairly ridiculous. Take Soul Eater for example. Originally broadcast in high def in Japan, episodes were subbed and sent to the streaming sites within a couple of days. Funimation took nearly a year after the original broadcast to start releasing the DVDs (in SD) here in the states. High-def legitimate versions of the series are still unavailable (nearly 3 years after the original broadcast).
Example 2: FLCL.. 6 episode series, 24 minutes each. Originally released here for $30 a disc, and each disc contained only 2 episodes. Do the math, and you end up paying around $0.63 per minute... At the same rate, the first season of the series "Fringe" would cost $630.00 instead of the $30 (approx) it's currently retailing for. Corporate greed and obscene levels of markup drive a lot of us to find other means of acquiring entertainment. It's gotten better recently, but still not on par with domestic releases.
Honestly, I've got a couple hundred legally purchased anime discs on my shelves. There's a lot more that I would purchase if it were available, but there simply no reasonable commercial means of acquiring it.
So when can I start applying for the jobs to do this sort of work? I can't seem to find any job openings on Microsoft's site that are even tangentially related to DNA and biotech.
Actually, as I was taught it (which, I will readily admit, could be wrong), Central Dogma is in fact the proper term, though the definition has been tweaked over time. Originally it stated something along the lines of, One DNA gene is transcribed into one RNA transcript, which is then translated into one protein. The discovery of antibodies threw that concept out the window. Variability in intron splicing and recombination means that a small handful of genes can yield a huge variety of protein products (See VDJ recombination). Yet another twist was added with the discovery of retroviruses which reverse the direction of transcription, turning RNA into DNA. Previously we had thought the central dogma to be unidirectional. The more we learn about life's mechanisms, the less surprised we are when exceptions to the rules are discovered. Evolution really is the ultimate hacker; constantly expanding the usefulness of very simple resources.
Sounds nice in theory, but it's not as easy as you make it appear. First of all, modifying a plant is far more difficult (due primarily to the cell wall) than modifying a bacteria or animal cell. Viral vectors are limited by transgene size and target species, and gene guns are somewhat of a crap shoot. Add in plants' very high tolerance for polyploidy and polysomy, and it becomes quite difficult to add in an effective kill switch.
So, major structural changes that would prevent cross-breeding are out because 1: the knockout/knockin transgenes are simply too large for available vectors. 2: pollination efficiency would likely drop through the floor, making it ultimately unsustainable. 3: assuming you used the structures of some existing species, you now have to worry about your other transgenes spreading to those species as well (admittedly, this is unlikely, but still needs to be considered). Artificial Chromosomes are out because plants will happily tolerate most all of the mismatch errors which would kill animal cells. Making a gene metabolically expensive so that it confers no evolutionary advantage (and thus would not be preserved in wild populations) is essentially asking your crops to fail. You could compensate with more fertilizer, pesticide and water, but the extra maintenance required would defeat the purpose of growing GM crops in the first place. Killswitch genes perhaps? They have plenty of their own problems too.
So, what mechanism would you propose?
TL;DR Breeding incompatibility with wild crops sounds nice in theory, but it's problematic to implement. Also, sorry if my rant is illogical/incoherent, It's the weekend, and my brain's on break as well.
First, I agree completely. I can't tell you how much time a program like that would save.
I'd just like to add in a quick feature request. It would be very nice if it could take the.ab1 files from sequenced clones and quickly align and compare them to the theoretical construct, and then indicate what needed to be done differently. For example, "your inserts are forming concatemers: adjust their concentration relative to the vector during the ligation step, or treat them with CAP (alkaline phosphatase)." or "this particular sequence has internal cut sites: use this restriction endonuclease instead."
The software that I'm using now does allow you to figure out situations like the above, but all it does is alignments; Analyzing the reasons why something didn't work out takes guesswork, and the comparisons prettymuch have to be done manually. For the concatomers example, I'd have to back to my original insert sequence, make a text document of the DNA sequence, import multiple copies into the program, reverse a couple of them (sense/anti-sense), and then manually align the second and third copies. It's very time consuming when it really shouldn't be.
'I'm interested in transitioning biology from being sort of a craft, where every time you do something it's done slightly differently, often in ad hoc ways, to an engineering discipline with standardized methods of arranging information and standardized sets of parts that you can assemble to do things.'"
To some extent, this is already done with common bacterial strains, and the plasmid vectors we already use. Most of the plasmids we use in the industry have specific sets of features such as multiple cloning sites, inducible repressors, ORIs, antibiotic resistance sites etc... You need a plasmid that has a kanamycin resistance gene, high copy number, will add a His tag to your product, and lacks cut sites for a particular restriction enzyme? It's likely in the catalogues already. And if what you're trying to assemble is already in the catalogues, it's a target that may not be worth pursing anyway, since you're unlikely to get a publication or a patent off of it.
The approach he seems to be pushing here seems to be analogous to buying a car piece by piece rather than as a pre-assembled package. The difference is that while average joe has no idea how to fabricate a synchro for his transmission, your average molecular biologist is already quite adept at designing primers and cloning fragments out of a cDNA library. The hard part for the scientists is then characterizing, validating and optimizing the expression of their target; and then later demonstrating the functionality of the product. To continue the analogy, it would be showing that the car ran, was reliable, and was safe for the passengers. Having readily available gene circuits (the famous lac operon for instance) may help with the planning and initial development, but it really won't speed up the bulk of the work we do.
I'll readily admit that many of the expression/knockout constructs are somewhat ad hoc in nature, but interoperability isn't typically a concern. The thing is that evolution is a pretty laissez faire system where "duct tape and bailing wire" construction is more often the rule than the exception. Nature cares about what works, not about what conforms to standards (codon-amino acid translation being the biggest exception that comes to mind). As a result, expression systems have to be tailored to the organism that they'll be expressed in. For instance, bacteria cannot express functional mammalian genes unless the introns are removed from the sequence first. Sufficiently large yeast proteins will cause an immune reaction because the glycosylation patterns are recognized as foreign. Many genes won't be expressed very well at all unless the regulatory elements in the flanking sequences are also included. Once you start looking at things like inducible expression and tissue-specific expression, things get even more complicated, and more varied between species. In short, it's complicated, and the idea of instituting standards to achieve interoperability between expression systems is pretty much a pipe dream.
In short, I have my doubts about the plausibility of this plan, and I'll be mighty impressed if he pulls it off.
I'm of the opinion that the person who coined the term "Junk DNA" did the field a disservice.
Much of the 'junk' DNA did serve a purpose at one point; deactivated genes for instance. Much of it still serves a purpose now, such as coding elements and transcription factors (see the work of Sean Carroll for more info on this point). Some of it is there for epigenetic and structural modifications such as the methylation of cysteine residues, (and similarly the acetylation of histones) which actually changes the shape of the DNA helix itself (and this affects transcription). And some of it is there simply to take up space. Intron splicing, for example, requires a minimum distance between the exons to function properly; longer is okay, but too short and you'll start skipping out on pieces of genes that *should* be there. And, following one of the older theories about the purpose of the 'junk' DNA, it acts as a buffer space to limit the damage caused by mutations that *will* happen.
So yes, the "junk DNA" isn't necessarily useless; but in many cases its sequence isn't necessarily meaningful either.
To use a car analogy: Sometimes it's like analyzing the composition of your engine block, where changes in the trace elements can have an affect of the performance of the vehicle as a whole. And sometimes it's analyzing samples of the air residing in your door panel (between the exterior sheet metal and plasticky interior) It's there to take up space and its composition really doesn't matter overall.
As I understand it, no. Since the change this produces is in the transcription/translation machinery of the cell, rather than in the DNA itself, the treatment is not permanent. Different substances are recycled in the cell at different rates (and nearly everything gets recycled at some point), with the cell rebuilding the parts that are in its genetic blueprints. Parts that aren't in the blueprints (i.e. the molecule that allows the gene to produce a protein product) do not get rebuilt. So the change is _not_ permanent.
Otherwise they would use an engineered virus to deliver the mutation to your entire body.
This is very unlikely to be used as a treatment any time in the near future. When gene therapy using viral vectors was introduced, there were several cases where it was quite successful. There were also deaths. Those deaths and the fear mongering that accompanied have created a social climate where very few people would acknowledge gene therapy as a valid treatment option.
Yes, I was incorrect. Please see the clarification I've since made. I'll accept the blame for having posted something for which I don't have sufficient justification or evidence. Feel free to mod down the original comment and the disinformation it contains.
Obviously this is all unconfirmed at best. and I still have some serious doubts about the story,
and
Again, this is all just rumors and lies at this point
And from my subsequent post
Okay, I need to get my facts straight. After doing some reading up on the topic (too late obviously) it is not clear to me that this guy's story was crap.
Now, what part of all that indicated that I "believe anything someone tells [me]?" I apologize if my post came across as if I were preaching doctrine from the mouth of God Himself, but I thought I was pretty clear that this was all speculation.
Okay, I need to get my facts straight. After doing some reading up on the topic (too late obviously) it is not clear to me that this guy's story was crap. The GM island *does* in fact exist as confirmed by WoWwiki. The islands are in fact, closed zones; Tel Abim and Zandalar specifically. The exploit to get these islands (here I go with the crazy theories again) is covered in a Thottbot post on the Levitate spell.
[...] I mounted, and as I lept off into the horizon, I casted levitate. I came to a point where the map disappeared, but the water continued to stretch out into the distance.
Some theorize that this is where GM Island is located.
Okay, so we all know that GM Island is in an instance now. But like any instance, there's a non-instance version of it. Like when you set old world instances to "Heroic" and walk behind the portals. GM Island wasn't always an instance, and programmers just don't delete environment from the game. Case in point, Old Ironforge and Ironforge Airport.
Granted, you'd have to walk pretty far, assuming GM Island IS in that direction...
Moving on, it's unreachable alone...attempted it. However, multiple priests together could do this easy. Have 5 or so in a group together so they can heal off of each other with renew and circle of healing. Another tip, wear +healing gear that has no stamina. Fatigue hits for 20% of your max health every 1-3 seconds. Low health means low damage, high healing means you can heal over it. 5 priests means you can have a few of them sit back and relax while the others cast, so not everyone wastes mana.
If you are really interested in doing this, make it 4 priests and a warlock.
"Harmonex wishes to summon you to GM Island."
[...]
Of course, this is all under the assumption that GM Island even exists on the main map...
There are also indications that early design work included some of the islands in this area,
It's true that a couple of islands appear on the map near the vortex. I heard a rumor about them once indicating that they were at one point accessible to players. Swimming there wasn't possible due to the fatigue that resulted from the deep water. However, if you had a couple stacks of elixirs of water walking, you wouldn't be affected by the fatigue since you weren't swimming. According to the one player I knew who had claimed to have been there, it took about 45 minutes of wandering around with nothing but waves in sight. Once he got to the island, he looted a chest that contained a full tier set of paladin gear. 20 minutes later his account had received a 72 hour ban, and all his recent loot had been removed from his inventory. His theory was that the island was a place where GMs could perform in-game testing of items and whatnot. Obviously this is all unconfirmed at best. and I still have some serious doubts about the story, but anyway, that's the only thing I've ever heard about the islands.
And just so that this post isn't entirely off topic, here's a link to some of the current speculation on the lore which will be experienced with the expansion. As an added note, it's doubtful that this will be the final expansion of the game. Most are speculating that there will be a 5th chapter in which players will get to enter the emerald dream. Again, this is all just rumors and lies at this point.
So which Petabyte are we talking about? The functional petabyte (i.e. 1,125,899,906,842,624 bytes), or the hard drive manufacturer's version( i.e. 1,000,000,000,000,000 bytes)?
Actually, a quick wikipedia search tells me that 10^15 is indeed the petabyte, while 1024^5 is the pebibyte. But according to Wikipedia I've been using the wrong terms this whole time anyway. kibibytes, mebibytes, gibibytes, tebibytes. etc... Somehow it all feels wrong now, and I want to blame Western Digital, or maybe Maxtor.
from Drs. Erick Janssen and Stephanie Sanders, both of the Kinsey Institute.
Erick: Hey Steph, I'll give you $100,000.00 if you sleep with me a few times. Stephanie: How many times is a few? Erick: Until we reach statistical significance. Steph: Cash? Erick: Sure.
Two weeks later, Erick pockets the other 300 Grand.
That's a bit like what happened when I tried to get my brother to switch to Ubuntu. When I called him later and asked him how it was working for him, he informed me that he had switched back to Windows.
His reason? "I couldn't get the antivirus to install."
As I understand it, the "objectionable" was referring to the lyrics in the music rather than fear of infringement by the copyright holder. Quoting from Engadget because I can't find the nin.com post:
As posted by Trent himself in response to Apple's rejection eMail:
...I'll voice the same issue I had with Wal-Mart years ago, which is a matter of consistency and hypocrisy. Wal-Mart went on a rampage years ago insisting all music they carry be censored of all profanity and "clean" versions be made for them to carry. Bands (including Nirvana) tripped over themselves editing out words, changing album art, etc to meet Wal-Mart's standards of decency - because Wal-Mart sells a lot of records. NIN refused, and you'll notice a pretty empty NIN section at any Wal-Mart. My reasoning was this: I can understand if you want the moral posturing of not having any "indecent" material for sale - but you could literally turn around 180 degrees from where the NIN record would be and purchase the film "Scarface" completely uncensored, or buy a copy of Grand Theft Auto where you can be rewarded for beating up prostitutes. How does that make sense? You can buy The Downward Fucking Spiral on iTunes, but you can't allow an iPhone app that may have a song with a bad word somewhere in it. Geez, what if someone in the forum in our app says FUCK or CUNT? I suppose that also falls into indecent material. Hey Apple, I just got some SPAM about fucking hot asian teens THROUGH YOUR MAIL PROGRAM. I just saw two guys having explicit anal sex right there in Safari! On my iPhone!
Come on Apple, think your policies through and for fuck's sake get your app approval scenario together.
Later in the threaded discussion, Trent clarifies his position with this little gem:
Everyone - let me be clear. I love Apple products and as goofy and out-of-touch as their app approval process / policy is, I will still use them because they work 1000X better than the competition. This is not a debate, it's a fact. The iPhone is THE most elegant, modern smartphone at this point in time and it's perfect for what we want to do with the NIN app - except for the ludicrous approval process, and that's what I want to draw attention to.
Android is cool, but nobody has an Android phone. Blackberry is OK but the hardware is inconsistent and WinMo straight-up sucks balls. If Apple doesn't get it together, we will most certainly make it available to the jailbreak community. I didn't invest in this app to see it languish on the sidelines from an idiotic policy while this tour is in full swing.
The nin.com front page currently has a link to download the app for those of you who are interested in it. Disclaimer: I'm not associated or affiliated with Engadget, the above quoting was simply convenient for posting purposes.
Slashdot Mirror
Okay, I really need to start reading TFAs and stop posting during the hours when I should already be asleep.
So as some have pointed out, there was no contract between Monsanto and the farmer in question. So this does go back to an IP infringement case, contrary to my previous post. However, I do stand by my previous statements regarding the need for refuge areas, and the need to monitor GM crops to ensure they are in compliance with refuge requirements. Consequently, the farmer in question is potentially dealing a regulated crop while flouting the associated regulations. But then again, I'm not privy to every detail of the case, and may as well be talking out of my ass.
As I understand it, the issue with the replanted/cleaned seeds is a matter of intentional breach of contract rather than one of patent infringement. When you purchase their seeds, you purchase a license with them that prohibits the replanting/cleaning of the seeds. So whether or not IP was infringed is essentially irrelevant to the stipulations of the contract itself.
Monsanto discusses the topic on their FAQ concerning Food Inc. http://www.monsanto.com/food-inc/Pages/default.aspx
There's also a practical reason behind preventing the cleaning and replanting of seed. Since these seeds contain a pesticide (Bt derivative), a necessary step to maintaining the efficacy of the pesticide is planting a refuge (non-GM section) as part of the crop. If the whole crop expressed the pesticide genes, we could expect resistance to develop very quickly, but by adding in refuge areas the selective pressure decreases. The size of the refuge varies depending on the mix of proteins being expressed, and is determined by the EPA. These non-GM refuge seeds are sometimes mixed in with the GM ones at specific ratios. By cleaning/replanting the seeds, the ratio of GM to non-GM seeds changes, and the size of the refuge is no longer controlled. This creates a situation similar to the over-prescription of antibiotics that we're all familiar with; resistant pest strains will appear much more frequently. So there are reasons other than simple greed behind these contracts.
Disclaimer: I'm currently employed at Monsanto, but contracted through a third party. I am not authorized to speak on behalf of the company, and my comments should not be interpreted as such.
Since there seems to be a bit of confusion here, allow me to explain (inadequately I'm sure) why different manufacturing processes for biologics result in non-identical molecules even though the DNA sequence and folding of the amino acids is the same.
One of the primary differences is in the glycosylation of the protein. This is where sugar groups of various structures are attached to the outside of the protein and act as a sort of label to the body (distinguishing self from non-self proteins), and even within the cell itself (identifying where the protein should be placed inside of the cell). Different organisms each have their own system for attaching and interpreting these sugar groups. For instance, typical yeast Saccharomyces cerevisiae has a glycosylation profile that will cause the human immune system to attack it eventually - which will make you have an adverse reaction not only to the drug that you're taking, but any other drug produced in the same organism. The yeast Pichia pastoris has a glycosylation profile that is superficially similar to a human one, making it less likely to cause an adverse reaction, but the organism is locked down by patents. Furthermore, there's some evidence that the glycosylation is affected by the health of the cells in the culture, and the media that you're culturing them in. Frequently we'll just coat the proteins in polyethylene glycol and hope for the best.
The other place that variation occurs is in the purification processes that are used to separate the drug molecules from everything else. Many of the purification processes will alter the glycosylation profile or the folding of the protein. They're also generally rather lossy, in that the purer the protein you want, the less of it you'll end up with, and the more it will cost. We used to attach tags to the proteins so that they were easier to purify (his6 was a common one), but then there were concerns that the tag itself would become the target for an immune reaction (which, like the glycosylation, would make a person resistant to not only the drug they were taking, but any other drug that used the same tag), so the practice has been mostly discontinued.
The simple fact is that biologics will always result in mixed batches of molecules, and different manufacturing processes do directly affect that mix. The trick for biosilmilars will be to ensure that their mix is functionally similar enough to the original one; which will likely require clinical trials - meaning that cost savings won't be nearly so drastic as it is with small molecule drugs. While we've figured out how to make DNA translate to a protein of our choosing, we're not nearly as knowledgeable about how to manipulate sugar groups in a similar manner. Progress is being made for sure, but we're not there yet.
There's a company called Argos therapeutics http://www.argostherapeutics.com/ which uses proteins harvested from cancer biopsies to do the same thing. Last I checked, they were in phase 2 clinicals (efficacy testing). This is as close to personalized medicine as anyone is really able to do right now. Disclaimer: the only tie to the company that I have is that I interviewed there a couple years ago (didn't get the job unfortunately).
As I understand it, the typical American has more debt than they do fungible assets. Inflation only means that they'll have less relative debt burdening them. Of course, there's a multitude of other less desirable consequences of hyperinflation, but I'm sure a competent marketing company could make the public welcome such changes.
Disclaimer: I'm not an Economist; not even one of the armchair variety.
I'll admit, it's technically not zero coverage. But assuming something rather severe happened to my health, I'm still faced with the choice to either A: die. or B: bankrupt both myself and my immediate family (as well as possibly my extended family) for the foreseeable future. Honestly, I'm not a cruel enough person to choose B. I know there are instances where the costs get covered, and I do personally know people that have had that happen, but I also personally know people who have been forced to sell their houses over medical debts of relatives.
Personally, I'm still rather irritated that a significant portion of my taxes went towards 'health care', and yet I still have zero coverage. I realize that this particular discussion has been beaten to death around here, so don't feel like you have to reply. I just want to complain about it somewhere.
In a lot of cases, I'd agree with you. Unfortunately, the release schedule stateside is fairly ridiculous. Take Soul Eater for example. Originally broadcast in high def in Japan, episodes were subbed and sent to the streaming sites within a couple of days. Funimation took nearly a year after the original broadcast to start releasing the DVDs (in SD) here in the states. High-def legitimate versions of the series are still unavailable (nearly 3 years after the original broadcast).
Example 2: FLCL.. 6 episode series, 24 minutes each. Originally released here for $30 a disc, and each disc contained only 2 episodes. Do the math, and you end up paying around $0.63 per minute... At the same rate, the first season of the series "Fringe" would cost $630.00 instead of the $30 (approx) it's currently retailing for. Corporate greed and obscene levels of markup drive a lot of us to find other means of acquiring entertainment. It's gotten better recently, but still not on par with domestic releases.
Honestly, I've got a couple hundred legally purchased anime discs on my shelves. There's a lot more that I would purchase if it were available, but there simply no reasonable commercial means of acquiring it.
So when can I start applying for the jobs to do this sort of work? I can't seem to find any job openings on Microsoft's site that are even tangentially related to DNA and biotech.
Actually, as I was taught it (which, I will readily admit, could be wrong), Central Dogma is in fact the proper term, though the definition has been tweaked over time.
Originally it stated something along the lines of, One DNA gene is transcribed into one RNA transcript, which is then translated into one protein.
The discovery of antibodies threw that concept out the window. Variability in intron splicing and recombination means that a small handful of genes can yield a huge variety of protein products (See VDJ recombination).
Yet another twist was added with the discovery of retroviruses which reverse the direction of transcription, turning RNA into DNA. Previously we had thought the central dogma to be unidirectional.
The more we learn about life's mechanisms, the less surprised we are when exceptions to the rules are discovered. Evolution really is the ultimate hacker; constantly expanding the usefulness of very simple resources.
Also, kudos on the evangelion reference.
Sounds nice in theory, but it's not as easy as you make it appear. First of all, modifying a plant is far more difficult (due primarily to the cell wall) than modifying a bacteria or animal cell. Viral vectors are limited by transgene size and target species, and gene guns are somewhat of a crap shoot. Add in plants' very high tolerance for polyploidy and polysomy, and it becomes quite difficult to add in an effective kill switch.
So, major structural changes that would prevent cross-breeding are out because
1: the knockout/knockin transgenes are simply too large for available vectors.
2: pollination efficiency would likely drop through the floor, making it ultimately unsustainable.
3: assuming you used the structures of some existing species, you now have to worry about your other transgenes spreading to those species as well (admittedly, this is unlikely, but still needs to be considered).
Artificial Chromosomes are out because plants will happily tolerate most all of the mismatch errors which would kill animal cells.
Making a gene metabolically expensive so that it confers no evolutionary advantage (and thus would not be preserved in wild populations) is essentially asking your crops to fail. You could compensate with more fertilizer, pesticide and water, but the extra maintenance required would defeat the purpose of growing GM crops in the first place.
Killswitch genes perhaps? They have plenty of their own problems too.
So, what mechanism would you propose?
TL;DR Breeding incompatibility with wild crops sounds nice in theory, but it's problematic to implement. Also, sorry if my rant is illogical/incoherent, It's the weekend, and my brain's on break as well.
First, I agree completely. I can't tell you how much time a program like that would save.
.ab1 files from sequenced clones and quickly align and compare them to the theoretical construct, and then indicate what needed to be done differently. For example, "your inserts are forming concatemers: adjust their concentration relative to the vector during the ligation step, or treat them with CAP (alkaline phosphatase)." or "this particular sequence has internal cut sites: use this restriction endonuclease instead."
I'd just like to add in a quick feature request. It would be very nice if it could take the
The software that I'm using now does allow you to figure out situations like the above, but all it does is alignments; Analyzing the reasons why something didn't work out takes guesswork, and the comparisons prettymuch have to be done manually. For the concatomers example, I'd have to back to my original insert sequence, make a text document of the DNA sequence, import multiple copies into the program, reverse a couple of them (sense/anti-sense), and then manually align the second and third copies. It's very time consuming when it really shouldn't be.
'I'm interested in transitioning biology from being sort of a craft, where every time you do something it's done slightly differently, often in ad hoc ways, to an engineering discipline with standardized methods of arranging information and standardized sets of parts that you can assemble to do things.'"
To some extent, this is already done with common bacterial strains, and the plasmid vectors we already use. Most of the plasmids we use in the industry have specific sets of features such as multiple cloning sites, inducible repressors, ORIs, antibiotic resistance sites etc... You need a plasmid that has a kanamycin resistance gene, high copy number, will add a His tag to your product, and lacks cut sites for a particular restriction enzyme? It's likely in the catalogues already. And if what you're trying to assemble is already in the catalogues, it's a target that may not be worth pursing anyway, since you're unlikely to get a publication or a patent off of it.
The approach he seems to be pushing here seems to be analogous to buying a car piece by piece rather than as a pre-assembled package. The difference is that while average joe has no idea how to fabricate a synchro for his transmission, your average molecular biologist is already quite adept at designing primers and cloning fragments out of a cDNA library. The hard part for the scientists is then characterizing, validating and optimizing the expression of their target; and then later demonstrating the functionality of the product. To continue the analogy, it would be showing that the car ran, was reliable, and was safe for the passengers. Having readily available gene circuits (the famous lac operon for instance) may help with the planning and initial development, but it really won't speed up the bulk of the work we do.
I'll readily admit that many of the expression/knockout constructs are somewhat ad hoc in nature, but interoperability isn't typically a concern. The thing is that evolution is a pretty laissez faire system where "duct tape and bailing wire" construction is more often the rule than the exception. Nature cares about what works, not about what conforms to standards (codon-amino acid translation being the biggest exception that comes to mind). As a result, expression systems have to be tailored to the organism that they'll be expressed in. For instance, bacteria cannot express functional mammalian genes unless the introns are removed from the sequence first. Sufficiently large yeast proteins will cause an immune reaction because the glycosylation patterns are recognized as foreign. Many genes won't be expressed very well at all unless the regulatory elements in the flanking sequences are also included. Once you start looking at things like inducible expression and tissue-specific expression, things get even more complicated, and more varied between species. In short, it's complicated, and the idea of instituting standards to achieve interoperability between expression systems is pretty much a pipe dream.
In short, I have my doubts about the plausibility of this plan, and I'll be mighty impressed if he pulls it off.
I'm of the opinion that the person who coined the term "Junk DNA" did the field a disservice.
Much of the 'junk' DNA did serve a purpose at one point; deactivated genes for instance. Much of it still serves a purpose now, such as coding elements and transcription factors (see the work of Sean Carroll for more info on this point). Some of it is there for epigenetic and structural modifications such as the methylation of cysteine residues, (and similarly the acetylation of histones) which actually changes the shape of the DNA helix itself (and this affects transcription). And some of it is there simply to take up space. Intron splicing, for example, requires a minimum distance between the exons to function properly; longer is okay, but too short and you'll start skipping out on pieces of genes that *should* be there. And, following one of the older theories about the purpose of the 'junk' DNA, it acts as a buffer space to limit the damage caused by mutations that *will* happen.
So yes, the "junk DNA" isn't necessarily useless; but in many cases its sequence isn't necessarily meaningful either.
To use a car analogy: Sometimes it's like analyzing the composition of your engine block, where changes in the trace elements can have an affect of the performance of the vehicle as a whole. And sometimes it's analyzing samples of the air residing in your door panel (between the exterior sheet metal and plasticky interior) It's there to take up space and its composition really doesn't matter overall.
I'm guessing that it's a one time treatment.
As I understand it, no. Since the change this produces is in the transcription/translation machinery of the cell, rather than in the DNA itself, the treatment is not permanent. Different substances are recycled in the cell at different rates (and nearly everything gets recycled at some point), with the cell rebuilding the parts that are in its genetic blueprints. Parts that aren't in the blueprints (i.e. the molecule that allows the gene to produce a protein product) do not get rebuilt. So the change is _not_ permanent.
Otherwise they would use an engineered virus to deliver the mutation to your entire body.
This is very unlikely to be used as a treatment any time in the near future. When gene therapy using viral vectors was introduced, there were several cases where it was quite successful. There were also deaths. Those deaths and the fear mongering that accompanied have created a social climate where very few people would acknowledge gene therapy as a valid treatment option.
because the parasite that causes malaria can't fully develop into the human pathogen outside of the mosquito (among other reasons).
Yes, I was incorrect. Please see the clarification I've since made. I'll accept the blame for having posted something for which I don't have sufficient justification or evidence. Feel free to mod down the original comment and the disinformation it contains.
Obviously this is all unconfirmed at best. and I still have some serious doubts about the story,
and
Again, this is all just rumors and lies at this point
And from my subsequent post
Okay, I need to get my facts straight. After doing some reading up on the topic (too late obviously) it is not clear to me that this guy's story was crap.
Now, what part of all that indicated that I "believe anything someone tells [me]?" I apologize if my post came across as if I were preaching doctrine from the mouth of God Himself, but I thought I was pretty clear that this was all speculation.
[...] I mounted, and as I lept off into the horizon, I casted levitate. I came to a point where the map disappeared, but the water continued to stretch out into the distance.
Some theorize that this is where GM Island is located.
Okay, so we all know that GM Island is in an instance now. But like any instance, there's a non-instance version of it. Like when you set old world instances to "Heroic" and walk behind the portals. GM Island wasn't always an instance, and programmers just don't delete environment from the game. Case in point, Old Ironforge and Ironforge Airport.
Granted, you'd have to walk pretty far, assuming GM Island IS in that direction...
Moving on, it's unreachable alone...attempted it. However, multiple priests together could do this easy. Have 5 or so in a group together so they can heal off of each other with renew and circle of healing. Another tip, wear +healing gear that has no stamina. Fatigue hits for 20% of your max health every 1-3 seconds. Low health means low damage, high healing means you can heal over it. 5 priests means you can have a few of them sit back and relax while the others cast, so not everyone wastes mana.
If you are really interested in doing this, make it 4 priests and a warlock.
"Harmonex wishes to summon you to GM Island." [...] Of course, this is all under the assumption that GM Island even exists on the main map...
There are also indications that early design work included some of the islands in this area,
It's true that a couple of islands appear on the map near the vortex. I heard a rumor about them once indicating that they were at one point accessible to players. Swimming there wasn't possible due to the fatigue that resulted from the deep water. However, if you had a couple stacks of elixirs of water walking, you wouldn't be affected by the fatigue since you weren't swimming. According to the one player I knew who had claimed to have been there, it took about 45 minutes of wandering around with nothing but waves in sight. Once he got to the island, he looted a chest that contained a full tier set of paladin gear. 20 minutes later his account had received a 72 hour ban, and all his recent loot had been removed from his inventory. His theory was that the island was a place where GMs could perform in-game testing of items and whatnot. Obviously this is all unconfirmed at best. and I still have some serious doubts about the story, but anyway, that's the only thing I've ever heard about the islands.
And just so that this post isn't entirely off topic, here's a link to some of the current speculation on the lore which will be experienced with the expansion. As an added note, it's doubtful that this will be the final expansion of the game. Most are speculating that there will be a 5th chapter in which players will get to enter the emerald dream. Again, this is all just rumors and lies at this point.
So which Petabyte are we talking about? The functional petabyte (i.e. 1,125,899,906,842,624 bytes), or the hard drive manufacturer's version( i.e. 1,000,000,000,000,000 bytes)?
Actually, a quick wikipedia search tells me that 10^15 is indeed the petabyte, while 1024^5 is the pebibyte. But according to Wikipedia I've been using the wrong terms this whole time anyway. kibibytes, mebibytes, gibibytes, tebibytes. etc... Somehow it all feels wrong now, and I want to blame Western Digital, or maybe Maxtor.
from Drs. Erick Janssen and Stephanie Sanders, both of the Kinsey Institute.
Erick: Hey Steph, I'll give you $100,000.00 if you sleep with me a few times.
Stephanie: How many times is a few?
Erick: Until we reach statistical significance.
Steph: Cash?
Erick: Sure.
Two weeks later, Erick pockets the other 300 Grand.
That's a bit like what happened when I tried to get my brother to switch to Ubuntu. When I called him later and asked him how it was working for him, he informed me that he had switched back to Windows.
His reason? "I couldn't get the antivirus to install."
Quoting from Engadget because I can't find the nin.com post:
As posted by Trent himself in response to Apple's rejection eMail:
...I'll voice the same issue I had with Wal-Mart years ago, which is a matter of consistency and hypocrisy. Wal-Mart went on a rampage years ago insisting all music they carry be censored of all profanity and "clean" versions be made for them to carry. Bands (including Nirvana) tripped over themselves editing out words, changing album art, etc to meet Wal-Mart's standards of decency - because Wal-Mart sells a lot of records. NIN refused, and you'll notice a pretty empty NIN section at any Wal-Mart. My reasoning was this: I can understand if you want the moral posturing of not having any "indecent" material for sale - but you could literally turn around 180 degrees from where the NIN record would be and purchase the film "Scarface" completely uncensored, or buy a copy of Grand Theft Auto where you can be rewarded for beating up prostitutes. How does that make sense? You can buy The Downward Fucking Spiral on iTunes, but you can't allow an iPhone app that may have a song with a bad word somewhere in it. Geez, what if someone in the forum in our app says FUCK or CUNT? I suppose that also falls into indecent material. Hey Apple, I just got some SPAM about fucking hot asian teens THROUGH YOUR MAIL PROGRAM. I just saw two guys having explicit anal sex right there in Safari! On my iPhone!
Come on Apple, think your policies through and for fuck's sake get your app approval scenario together.
Later in the threaded discussion, Trent clarifies his position with this little gem:
Everyone - let me be clear. I love Apple products and as goofy and out-of-touch as their app approval process / policy is, I will still use them because they work 1000X better than the competition. This is not a debate, it's a fact. The iPhone is THE most elegant, modern smartphone at this point in time and it's perfect for what we want to do with the NIN app - except for the ludicrous approval process, and that's what I want to draw attention to.
Android is cool, but nobody has an Android phone. Blackberry is OK but the hardware is inconsistent and WinMo straight-up sucks balls. If Apple doesn't get it together, we will most certainly make it available to the jailbreak community. I didn't invest in this app to see it languish on the sidelines from an idiotic policy while this tour is in full swing.
The nin.com front page currently has a link to download the app for those of you who are interested in it.
Disclaimer: I'm not associated or affiliated with Engadget, the above quoting was simply convenient for posting purposes.
This VG Cats comic seemed pertinent to the topic. No I'm not affiliated in any way. http://www.vgcats.com/comics/