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Comment similar tech using proteins instead of genes (Score 1) 209

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).

Comment Re:Inflation (Score 1) 696

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.

Comment Re:Posted AC, any Biologists here? (Score 1) 550

This isn't a topic that I'm honestly all that familiar with (neither the lab in a box nor HGH specifically), but I can offer some speculation.

For HGH, you're lucky in that it's actually a protein, since producing proteins with a specific structure is relatively straightforward. To grow your own, you'll need the gene in a plasmid or some other vector. For a eukaryotic host (CHO or yeast typically), you can clip the gene out of any human cell and put it in (this is far more difficult than I'm making it sound). For a prokaryotic (bacterial) host, you'll need to extract RNA from pituitary gland cells, make cDNA, and then insert that into the vector. Prokaryotic hosts are easier to work with, but do present problems with the immunogenicity of the end product; eukaryotic hosts are generally less stable over several generations and pickier about their growth conditions, but do generally provide the post-translational modifications that will keep the stuff from making you sick. Chances are that someone has already constructed a plasmid with the gene in it; which can save you a lot of effort. Get the plasmid with the gene, pop it into a suitable host, and start growing it. Purifying it afterwards can be simple or complicated, and unfortunately that's not my area of expertise. Growing the organism could be done in shake flasks, which would put it well within the capabilities of a DIYer, but purifying is more complicated. Your best bet for purifying is to use a protein A column loaded with anti-HGH antibodies, and then doing an acid elution to pull the product off the column. It's not cheap, and it's easy to mess up, but it can be done. Again though, purification isn't my area of expertise.

Now, concerning the lab in a box, the idea does sound rather appealing. What you have to realize is that synthesizing a DNA construct, getting it into a microbe, and then getting the microbe to grow while maintaining that construct are 3 different processes. Right now, for most of the oligos, primers, and other DNA constructs we need, we outsource the synthesis. Short ones (20bp or so) come back quickly, but a custom 170bp sequence that we designed took around 3 weeks to be delivered. HGH has 191 amino acids, which means that the DNA sequence is 573 base pairs long; minimum. The longer the sequence, the more likely the chances of introducing errors, and the longer it will take to synthesize in usable quantities. If there's not too many introns in the gene, PCRing it out would be the approach that I'd take, but that would add unnecessary complexity to the lab in a box concept. Anyway, before this turns into too long of a rant, the problem that you're still going to run into is in purifying the resulting protein. Some proteins are easier to purify than others, and there are some ways to make it easier (his6 tags for instance), but I'd still be very hesitant to use anything produced this way as a therapeutic. Still, a system that could pop out a microbe with a specific transgene would be very useful. For simple genes, yeah, I'd think it would be fairly plausible. If you want to synthesize something complex though such as chaperonins, or molecules that require extensive post translational modifications, I can't imagine anyone pulling it off without a firm understanding of the underlying molecular biology. Hopefully I've answered your questions.

Comment Re:Posted AC, any Biologists here? (Score 4, Interesting) 550

Biologist here, and currently employed by a major pharma company.
From what I've seen, the major cost in developing new treatments is in clinical trials. The R&D work is comparatively cheap. The major obstacles for a DIYer in developing a treatment are 1: producing and purifying enough of the substance to test. 2: demonstrating that the treatment is safe (phase 1 of a clinical trial) and 3: demonstrating that the treatment is effective (phase 2 of a clinical trial). As a DIYer, the typical clinical trials can be supplanted with trials in animal models (if available) until a major pharma company buys it up to fund the actual trials. The process can be expedited a little bit if you get what's known as "Orphan Drug Status" (i.e. nobody else is working on this illness since there's probably no money in it) which can grant you additional funding, and streamlines the FDA's approval process; but it's still not a guaranty of any sort.
Now, if a DIYer comes up with an effective treatment, and can produce it consistently at reasonable concentrations, then open-sources the formulation and production method, I'd still expect the FDA to step in to try and regulate it. Concerning your penicillin example, even though the molecule and production methods are well known, it's not something that the average joe can produce at home (not at therapeutic doses anyway), and it's still not something that can be sold over the counter. DIY biotech therapeutics is a good starting point, but it won't get to market without FDA approval, which, thanks to the cost of clinical trials, basically requires corporate sponsorship.

Comment Re:"Health Care" (Score 1) 642

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.

Comment "Health Care" (Score 2) 642

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.

Comment Re:Pirated copies are good for viewing... (Score 1) 199

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.

Comment Re:Central Dogma? (Score 4, Interesting) 196

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.

Comment Re:What? (Score 1) 414

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.

Comment agreed! (Score 3, Interesting) 71

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.

Comment Plasmids kinda do this already. (Score 2, Interesting) 71

'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.

Comment Re:"Junk" DNA (Score 1) 360

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.

Comment Re:A bit unclear to me... (Score 1) 360

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.

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