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Guest Post: The Genetics Of Investing - Kill The Messenger
Submitted by Doug Hornig of Casey Research
The Genetics Of investing - Kill The Messenger
If you had a previously incurable genetic condition and scientists
came up with a treatment for it, you’d jump at the chance to take
advantage. That’s a no-brainer. But what if you had the opportunity to
invest in a company deeply involved in just such cutting-edge research?
In classical drama, as well as real life, the bearer of bad news is
often executed, simply for having brought it; in modern medicine,
though, messenger killing is not only acceptable, it represents a major
breakthrough in our approach to genetic disorders.
And major may be a vast understatement. We’re talking about a
development that could not only revolutionize an entire field and save
countless lives, but one that will make fortunes for savvy investors.
It boils down to this: Scientists now have a technique for selectively,
and reversibly, turning off the behavior of certain pieces of the
genetic code in humans. The key word being reversibly.
Ever since the mapping of the human genome in recent years, researchers
have been digging ever deeper into the genetic causes of many
diseases. The idea was simple: find the gene responsible for a malady,
then alter or remove it from a person’s body and cure the disease. A
severe course of action, but one many patients were willing to risk for
the chance to cure a dreadful condition. In the 1990s, using a number
of techniques collectively known as gene therapy, doctors started
putting these new treatments into practice.
But the gene therapy route involves genetic mutation, a risky
proposition at best... After you’ve deconstructed the gene, you can’t
put it back together if problems develop, which they often did. The
genetic manipulations that were performed unleashed all kinds of side
effects – many of them lethal. Too many people were dying, so scientists
began looking beyond full-bore genetic assaults.
There had to be a better way, and there is…
The current preferred alternative – as yet still in its infancy – is
about as close to the polar opposite of the old approach as possible.
It doesn’t touch the gene at all. It’s not only temporary and easily
reversible, and thus good for the patient’s peace of mind, it’s also
well suited for experimentation on outside threats such as cancer, or
possibly even bacterial and viral infections.
It’s called RNA interference (RNAi), and as the name
implies, the technique involves interrupting the function of RNA
(ribonucleic acid), one of the key components of all living cells. In
order to understand exactly how it works, you first have to know just a
little about an extraordinarily complicated subject, human cell
dynamics. Here’s the short version.
At the center of the cellular action is the familiar,
twisted-ladder-shaped double helix structure known as DNA
(deoxyribonucleic acid). It consists of two very long chains of
molecules (polynucleotides), paired together. One chain is called the sense strand; its complement on the other side is called the anti-sense strand.
DNA is further subdivided into 23 chromosomes, and they in turn are sliced into about 25,000 smaller bits called genes.
Genes are the source of all top-level commands in the body. They direct
the production of proteins that make everything run smoothly or, in the
case of a genetic malfunction, run amok. And they do it through a
two-part process, transcription and translation.
First, transcription: Crawling all over the DNA are enzymes, little
ladder-climbing robots that dock at the boundaries between genes. Once
an enzyme locks on, it transcribes the code of a gene into a
particular form of single-stranded RNA (or one half of a tiny piece of
DNA). This RNA is always derived from the DNA’s sense strand. It mimics the gene that encoded it, except for a small chemical marker that designates it as a “messenger” RNA (mRNA), a sort of carrier pigeon used to send genetic instructions from the command center of a cell to its parts.
Then, translation: The enzyme releases the mRNA, and it travels to another part of the cell, the ribosome, a kind of all-purpose life-maintenance factory. It’s the ribosome that translates
the instructions carried by the RNA and starts building proteins – the
essential chemicals that support a healthy body – in accordance with
the underlying DNA command.
Message sent; message received.
However, when the ribosome’s protein production is not working
correctly or is genetically faulty to begin with, the body essentially
turns on itself. The mRNA is carrying the wrong message. This results
in diseases that have been very difficult to treat compared with their
virus- or bacteria-based counterparts.
Historically, fighting those diseases has been a matter of isolating
the offending protein and neutralizing it. No small feat. There are
about a hundred thousand different proteins in the body, interacting
with each other in billions of ways. And once you find the one you’re
looking for, you have to test compound after compound against it,
trying to identify the haystack needle that actually affects it (if
there is one). Modern high-speed computers have simplified this random
task, but it’s still incredibly time consuming.
Now all that’s changing – and the change is producing one of the most exciting developments in medicine today: anti-sense technology.
Once genetic mapping became a reality, researchers quickly discovered
that it was possible to sabotage wayward mRNA before it ever gets to
the ribosome. All you had to do was synthesize the anti-sense form of the undesirable mRNA and inject it into the cell, where it would bond with the sense
sequence automatically, effectively “switching off” the message. If
the ribosome can’t read it, you’ve achieved RNA interference, and the
offending proteins will never be produced at all.
You’ve killed the messenger.
That’s excellent in itself. But the added bonus is reversibility. The
effect lasts only as long as the anti-sense agent is present. If
counterproductive complications arise, you simply stop treatment and
the mRNA is returned to its previous state, once the supply of reacting
chemicals is exhausted.
It works. But establishing the theoretical basis, then proving it out,
those were the easy parts. Next came the difficulties, which divide
into two broad areas.
Of these, the toughest is that you need a pinpoint delivery system.
It’s obviously impossible to inject the anti-sense compound into
individual cells, one by one. Maybe in a Petri dish. But not in a human
being.
Then, once you do get it inside, you have to protect it from the body’s
natural defenses against invaders. After that, it must encounter its
target. Finally, it must align itself properly with the elaborately
folded RNA and generate the enzymes that will deactivate it.
Thus there’s a furious arms race underway, with plenty of companies
vying to develop the gold standard in delivery systems. So far, there’s
no clear winner – though it looks like multiple options for delivery
will eventually be available to therapy manufacturers, as recent
successes using lipids and polymers to deliver anti-sense molecules in
humans have demonstrated.
The other half of the equation is the need for the proper anti-sense
sequences. But before you can synthesize them, you have to identify
proteins associated with different diseases. That can be tricky.
Protein signatures differ among diseases, and can even differ among
patients with the same disease.
Zeroing in on the right target protein is not enough, either. You have
to then backtrack to the mRNA that causes its production. Only then can
you design your anti-sense messenger.
It’s not high school lab work, but still... Lock down on the right mRNA
and you don’t need to bombard it with randomly chosen compounds. You
only have to design one that features a complementary structure –
properly combining the four simple molecules that are the building
blocks of all DNA – and you’re done. Comparatively, it’s a walk on the
beach. Not to mention that you don’t have to tinker with the underlying
gene, either.
Hand-crafted cures for nearly every genetic malady, possibly extending
even to non-genetic ones – that’s the promise. If only we didn’t have
to wait for a reliable delivery system to make its way through the
scientific process and the regulatory gauntlet. But we do. In the
meantime, however, researchers are taking great strides forward with
mRNA identification and the development of specific anti-sense
molecules. There’s no reason not to stockpile them against the day when
they can easily be applied.
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I'm really not trolling here, I promise.
I'd be skeptical of a company like that. For every ten companies making strides in this kind of research, only one of them actually make money off of it.
The thing about it is that the company that does the R&D and gets invested in either gets bought by bigger fish later (which would be good for an investment) but most likely their company fails before it makes money.
Then the scientists with the knowledge go onto other companies, and the investors hold the bag.
Technology Review did a great piece on why certain ideas are monetizeable and other are not (I think two issues ago). Often times it takes a few cracks and failures before commerical success follows, but I remain hopeful in Biotech that we have not even seen a drop of the potential health (and commercial) benefits.
still it would take a good decade before we could see some real life application
(and even maybe a new kind of bio-weapon)
"new kind of bio-weapon"
i've been hanging out here too long...
i immediately thought about the other edge of that sword as well.
guns don't kill, peop...
Doug Hornig RNA interference (RNAi) is already old technology. Do yourself a favor and do some research on Zinc finger nucleus.
Zinc finger nucleus is the next genomic platform. It can knockout any gene in any organism at any time. Sangamo Bioscience (SGMO) has all the patents and has a stranglehold on the IP. They have licensed the technology to Dow Agro science to compete head to head with Monsanto, and have also licensed the technology to Sigma-Aldrich. They have two very interesting HIV phase 1 trials going on right now, and a few phase II trials.
I was disappointed to discover that the opposite of the sense strand was not the 'nonsense' strand.
That would have helped explain, e.g,. Bill Kristol, Wolfowitz, Greenspan and the rest of the jelly-brained morons who call each other 'genius'.
(Note - I did not intend for the above list to include only members of a certain penis-mutilation cult... so add Blair, Howard, Cheney, Condoleeeezzzaaa and von Rumsfeld to gentile-ify the list a bit).
Cheerio
GT
It was also good to learn that the Liberal DNA has been identified.
A parasitic mutation of the Antigen. Obama, Clinton(s), Gore, Frank, Reed, Dodd and Pelosi are all carriers. They must be stopped from reproducing. A clever high tech device has been uncovered in France, the Guilloutine. Ha!
Let us hope these carriers can be purged from the system quickly and recycled (the Green thing to do) as biohazardous waste.
This is old news. The research is promising, but this is still in its infancy.
Holy shit my head is spinning from reading that recombinant DNA theory r ribonuclearicacid something or another. Just give me the economics, stats, and numbers next time please?
Can someone provide names of companies that are involved in this area of research?
<... now putting tin hat back on...>
Can we do the same genetic reversal on the brains of those wizards that led us to where we are?
Corporate propaganda nonsense. There are so many factual errors in this post that it is essentially useless. Not all problems are fixed by turning the gene off (most aren't). Cancer is a valid target for such an approach but, there are literally hundreds of ways to manipulate genes to turn them on or off. The problem is always getting the treatments into the proper cells (and not others). Zinc finger nucleases (not nucleus) has the same delivery problem as RNAi.
All hype, 2 decades away from really having any clinical application.
http://maxkeiser.com/
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[KR76] Keiser Report – Markets! Finance! Extradition! September 9th, 2010 by stacyherbertRespond
Stacy Summary: We look at the scandals of no fiscal or monetary bullets left in the bankrupt warfare states of America. In the second half of the show, Max talks to Huffington Post blogger, Mike Jensen, about his call for Americans to unite against the emergency in their nation.
Everytime I read an article about RNAi, I want to barf. I held on to about 20k shares of a company called Sirna Therapeutics for a little less than two years because I was convinced that RNAi really was the next big thing. I gave up and dumped them a couple months before Merck bought them for a really substantial premium. I coulda been a thousandaire... C'est la vie.
Too many people were dying from gene therapy? Really?
And then there is the possibility that the current administration or religious right might take offense to changing the building blocks of life.
Thinking about stem cells (STEM) that I lost my a** on in '2000 after "W" took office.
They only stopped =federal= money going to =fetal/embryonic= stem cell development, which is not where the action was, nor where the action is, and very concretely so. The lefty whining, and MSM media relaying their every protest, regarding this extremely narrow, very nearly scientifically irrelevant issue, was opportunistic anti-republican, statist/marxist propaganda, existing 95% to weaken the opposing political party, and maybe 5% to further the proabortion extremism of the truly sick kooks on the left.
Notice the issue has gone away for them now that Democrats are in power following almost exactly the same policies, with approximately the same good reasons(embyonic stem cells are not the paydirt stem cell research area anyway, because plenty of stem cells can be directly obtained from adult subjects afflicted with any disease, providing perfect genetic match to the host!!!).
Note also that the anti-war left(Sheehan and Cie) has calmed down 10x and disappeared 1000x from the airwaves now that Barack the Destroyer is out there ordering US citizens killed(which I'm OK with, don't get me wrong), all-out drone strike wars in Pakistan(and oh, how am I OK with that), and tripling down in Afghanistan(horrendously stupid AND evil in the same go).
well written educational information. thanks
You auto not buy auto-robo-immunizing, RNAi silver bullets now. I pitched a similar story like the one above to a bleeding-edge RNAi researcher in the family and was told:SLOW DOWN- any cure for anything is years and years in the future and every disease will be addressed with its own, slow to prove-out process through years of lab testing, etc. Think LASIK investment hype and you're probably in the right mode of skepticism. There are firms claiming to have quick'n easy blood systems delivery all wrapped up, waiting for the right protein-blockers to be added. That's another "not so fast" solution for investors.
If you want to think 25 year warrant on a fledgling technology, a small position would be logical. Anything much grander would be a lottery-like speculation.
First of all, I promise you in advance that I'm not attempting to troll here, and also that I am not trying to start a flame war.
1. My first thought is that these kinds of processes are WEAPONIZABLE. In other words, these concepts can be -- and almost certainly WILL be -- the weapons of the future if they ever become successfully developed.
2. The terrorism implications are profound.
If these technologies ever become real, you can pretty much bet every Dollar you have that EVERY SINGLE NATION ON EARTH will develop weapons based upon the ideas here -- a weapon which can genetically induce something as simple as an inability to process sugar will place you into a coma very quickly -- and kill you within a day.
Release that into a city... well, you get the idea.
X-men, bitchez!
Thank u, i found this for a long time.
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