Tuesday, December 29, 2009

Things that make you go 'hmmn.'

Greetings good citizen,

Science isn’t for everyone (as evidenced by the dreck Hollywood continues to produce by the bucketful. Who funds this crap anyway?)

Um, if you’d rather perform your own dental work than be assaulted by news from today’s ‘scientific frontier’ then this article won’t be to your liking…but that does nothing to alter the ‘likely outcome’ of this kind of research.

Yes good citizen, I am often astonished by the mind-numbing lack of curiosity displayed by the average individual (not that I particularly blame them…so far technology has primarily been used to make things more difficult rather than easier. Your ‘solitude’ was the first item to be sacrificed on the altar of ‘high tech’, your ‘privacy’ followed immediately behind, for those of you who (mistakenly) think solitude has no value…)

Um, we are about to engage in a ‘word substitution’ game, something it is critical for you to understand because none of this makes sense if it is taken solely in its highly ‘altruistic’ frame of reference.

Every time you read the word ‘disease’ I want you to substitute the word ‘death’, because this is what they’re really after. It is the very real, present day continuation of a search that has been going on since before the Conquistadors and Ponce de Leon…

Um, why should you care what the very rich are funding with their money? I think you’d be very naïve to believe that the taxpayer isn’t the principal backer of this research through ‘block grants’ made to our nation’s university system…

Which brings us full circle to the real issue here, if the ‘secret of immortality’ is discovered (understand, this is the ‘end result’ of defeating death.) then who gets to partake? What is the determining factor that makes one ‘worthy’?

The public funded the research but the only publicly funded research that has produced ‘free’ benefits is flu research…and even those ‘free’ flu shots are paid for by the government…after the government hands over its bought and paid for research to ‘private’ drug companies for nothing…

Which is another CF altogether, but you see where I’m going with this.

Um, there is an even darker side to this conundrum so I’ll ask you directly; would you be willing to throw your fellow humans ‘under the bus’ in exchange for your shot at ‘immortality’?

The whole world looks very different when you start looking at it through the ‘lens of forever’.

Which begs a more interesting question: who do you want to share ‘eternity’ with?

[Um, if you think this would make a great plot for a novel you’re too late, I wrote it nine years ago!]

In New Way to Edit DNA, Hope for Treating Disease

Published: December 28, 2009

Only one man seems to have ever been cured of AIDS, a patient who also had leukemia. To treat the leukemia, he received a bone marrow transplant in Berlin from a donor who, as luck would have it, was naturally immune to the AIDS virus.

If that natural mutation could be mimicked in human blood cells, patients could be endowed with immunity to the deadly virus. But there is no effective way of making precise alterations in human DNA.

That may be about to change, if a powerful new technique for editing the genetic text proves to be safe and effective. At the University of Pennsylvania, Dr. Carl June and colleagues have used the technique to disrupt a gene in patients’ T cells, the type attacked by the AIDS virus. They have then infused those cells back into the body. A clinical trial is now under way to see if the treated cells will reconstitute a patient’s immune system and defeat the virus.

The technique, which depends on natural agents called zinc fingers, may revive the lagging fortunes of gene therapy because it overcomes the inability to insert new genes at a chosen site. Other researchers plan to use the zinc finger technique to provide genetic treatments for diseases like bubble-boy disease, hemophilia and sickle-cell anemia. [Time to expand on the idea of what makes ‘death’ a treatable disease; your body’s built-in ‘self-destruct’ mechanism, something most of you are ignorant of.]

In principle, the zinc finger approach should work on almost any site on any chromosome of any plant or animal. If so, it would provide a general method for generating new crop plants, treating many human diseases, and even making inheritable changes in human sperm or eggs, should such interventions ever be regarded as ethically justifiable. [True, ‘ideally’ you’d be born without a ‘self-destruct’ system, but most people’s self-destruct mechanism doesn’t activate until they reach ‘sexual maturity’…sort of gives a whole new meaning to the term ‘coming of age’.]

Zinc fingers are essential components of proteins used by living cells to turn genes on and off. Their name derives from the atom of zinc that holds two loops of protein together to form a “finger.” Because the fingers recognize specific sequences of DNA, they guide the control proteins to the exact site where their target gene begins. [False impressions are easy once you start playing in the realm of ‘theoretical possibility’…in ‘theory’ turning off your built in self-destruct mechanism would enable your body to repair itself, er, perfectly, um, forever. The ‘false impression’ comes in defining what you have actually achieved, which is best described as beating death by ‘natural causes’ rather than the much more certain ‘bullet proofing’ which would defeat death in all of its manifestations. (Near) immediate ‘re-generation’ is another ball of wax entirely and will probably be a long time coming, if ever.]

After many years of development, biologists have learned how to modify nature’s DNA recognition system into a general system for manipulating genes. Each natural zinc finger recognizes a set of three letters, or bases, on the DNA molecule. By stringing three or four fingers together, researchers can generate artificial proteins that match a particular site. [What we don’t know good citizen is what they are already capable of…did you know that color television existed (in military research facilities) prior to WWII?]

The new system has been developed by a small biotech company, Sangamo BioSciences of Richmond, Calif., and, to some degree separately, by academic researchers who belong to the Zinc Finger Consortium. [Note the ‘public/private’ aspects of this, er, ‘partnership’…]

Sangamo was founded in 1995 by Edward O. Lanphier II, a former executive with a gene therapy company. Reading an article by Aaron Klug, the British crystallographer who discovered the zinc finger design, he saw the technique’s potential for genetic manipulation. He bought a company Dr. Klug had founded and worked with him and researchers like Carl O. Pabo to improve the technique and develop combinations of zinc fingers to match any sequence of DNA letters.

“We now have a full alphabet of zinc fingers,” Mr. Lanphier said, “but when we started the company it was like typing a novel with two fingers.”

Zinc finger proteins have many potential uses. One is to link them to agents that turn on or turn off the gene at the site recognized by the fingers.

More powerfully, the zinc fingers can be deployed as a word processing system for cutting and pasting genetic text. Two sets of zinc fingers are attached to a protein that cuts the DNA in between the two sites matched by the fingers. The cell quickly repairs the break but sometimes in a way that disrupts the gene. This is the approach used in destroying the gene for the receptor used by the AIDS virus to gain entry to white blood cells. [Ho Ho! What a ‘useful trick’ this will turn out to be!]

Or, if DNA for a new gene is inserted into a cell at the same time as the zinc fingers that scissor the DNA, the new gene will be incorporated by the cell’s repair system into the DNA at the break site. Most gene therapy techniques use a virus to carry new genes into a cell but cannot direct the virus to insert genes at a specific site.

“I think it’s a broadly applicable technology that has already allowed experiments that would not have been possible before,” said J. Keith Joung, a biologist who designs zinc finger proteins at the Massachusetts General Hospital.

Daniel F. Voytas, a plant geneticist at the University of Minnesota, said the zinc finger technique would allow breeders to change the oil composition of any plant, the types of carbohydrates produced or the way carbon dioxide is captured. “We can go in and make any change we want to any plant species,” Dr. Voytas said. [You can be sure he doesn’t mean ‘any’ literally, at least at this stage of the game…but that’s the question, isn’t it? We don’t know for sure where they really are…]

Zinc fingers can also be used for “trait stacking,” the positioning of several beneficial genes at a single site. This avoids heavy regulatory costs because genetically altered plants must be tested for safety for each site that is modified.

The zinc finger technology has taken many years to prepare because of the difficulty of designing the fingers and also of preventing them from cutting the genome in the wrong places. Only a handful of laboratories are currently using the technique, but proponents expect to see rapid growth.

The Zinc Finger Consortium, founded by Dr. Joung and Dr. Voytas, makes the method available free, and researchers need only pay for materials. But there are some 200 steps in Dr. Joung’s recipe for making zinc fingers, and it takes time and dedication to do them all correctly. [Perhaps we don’t want to know what happens if you DON’T do them correctly…yet another question without a good answer.]

The alternative is to buy zinc fingers. Sangamo has a commanding patent position and has licensed Sigma-Aldrich, a large life science company in St. Louis, to make zinc finger proteins for researchers. Sigma-Aldrich’s charge for a zinc finger protein that cuts the genome at the site of your choice is $39,000, with a discount for academic researchers. Zinc fingers that cut well-known human genes cost $12,000. Sigma-Aldrich has used the technology to generate rats with genetic defects that mimic human disease. A schizophrenic rat can be had for $100. [Um, I’m sure you can get all the schizo-rats you want for nothing on Wall Street…]

David Smoller, president of Sigma-Aldrich’s biotechnology unit, licensed the technology from Sangamo in 2006 when he felt the company had proved it worked. “This technology is just amazing,” Dr. Smoller said. “It’s a game changer.” [Which leads us to wonder how much the game is already changed?]

Sangamo has licensed the use of zinc fingers to Dow Agrosciences for creating new crop plants, and has reserved medical uses for itself. It has four Phase 2 clinical trials in progress, including treatments for diabetic neuropathy and amyotrophic lateral sclerosis.

In an ambitious effort to cure AIDS, Sangamo and the University of Pennsylvania started a clinical trial in February. [Now there’s a treatment that would prove quite lucrative, although we still seem to be looking at the old ‘how much would you pay to save your life?’ proposition.]

The AIDS virus enters the T cells of the immune system by latching on to a receptor called CCR5, but about 10 percent of Europeans have a mutation that disables the CCR5 gene. People who inherit two disabled copies of the gene do not have CCR5 on the surface of their T cells, so the AIDS virus has nothing to grab. These people are highly resistant to H.I.V.

In the zinc finger approach, the patient’s T cells are removed, and zinc finger scissors are used to disable the CCR5 gene. The treated cells are allowed to multiply, then reinjected into the patient. In experiments with mice, the treated cells turned out to have a strong natural advantage over the untreated ones, since those are under constant attack by the AIDS virus.

Whether or not zinc fingers will make gene therapy practical remains to be seen. “It’s a little too early to know since clinical trials are in their early stages,” said Dr. Katherine A. High, a hemophilia expert at the University of Pennsylvania.

Dr. Matthew H. Porteus, a pediatric geneticist at the University of Texas, said, “I think it has the potential to solve a lot of the problems that have plagued the gene therapy field.” But Dr. Porteus noted that even the most carefully designed zinc fingers seemed to do some snipping away from their target site, a potentially serious safety problem. [Therein lies the ‘downside’ of playing with ‘the building blocks of life’. There is the potential to do more harm than good, like in the film ‘I am Legend’.]

Zinc fingers could be the gift that stem cell researchers have been waiting for. Stem cells taken from a patient may need to be genetically corrected before use, but until now there had been no way of doing so.

Dr. Rudolf Jaenisch, a stem cell expert at the Whitehead Institute in Cambridge, Mass., reported in August that he had successfully singled out three genes in induced embryonic stem cells with the help of zinc finger scissors designed by Sangamo. “This is a really important tool for human embryonic stem cells,” Dr. Jaenisch said. The technology has not yet reached perfection. Some of the zinc fingers Sangamo provided “worked beautifully,” he said, but some did not.

Zinc fingers may also make technically possible a morally fraught procedure that has been merely a theoretical possibility — the alteration of the human germ line, meaning the egg or sperm cells. Genetic changes made in current gene therapy are to body cells, and they would die with the individual. But changes made to the germ line would be inherited. Many ethicists and others say this is a bridge that should not be crossed, since altering the germ line, even if justifiable for medical reasons, would lower the barrier to other kinds of change. [Here there be monsters…and not just the creepy crawlies that infest the silver screen! Would you ‘suffer’ serious mutation as the price of immortality? Would you let them replace your skin with bullet-proof ‘Rhino hyde’? Or would you let them imbed horns or tusks on you, or perhaps poisonous fangs? Understand that once you ‘sign up’ for these ‘modifications’ you are by default ‘surrendering your humanity’ for their protection. Sounds ‘attractive’ on the surface but understand they won’t make the ‘mistake’ of making you ‘invulnerable’, they’ll kill you for sure if they think you’re too tough to manage. They’ll have the upper hand and you’ll know it…’nice’ is for appearances sake only, they don’t want the masses to ‘know’ they are evil incarnate.]

Several scientists were reluctant to discuss the issue, or dismissed it by saying that even zinc fingers did not meet the error-free standards that would be required for germ-line engineering. But zinc finger scissors are so efficient that only 5 to 10 embryos need be treated to get one with the desired result. This could make it practical to alter the germ line.

Since the germ lines of rats and zebra fish have already been altered with zinc finger scissors, “in principle there is no reason why a similar strategy could not be used to modify the human germ line,” Dr. Porteus said. The kind of disease that might be better treated in the germ line, if ethically acceptable, is cystic fibrosis, which affects many different tissues.

The disease could be corrected in unfertilized eggs, using the zinc finger technique, Dr. Porteus said. But he added, “I don’t think our society is ready for someone to propose this.”

Honestly now, how many of you were aware that modern science was capable of doing the procedures outlined in this article? If you’re not a genetic engineer, I’m going to guess very few of you.

Indeed, some of what they share here appears to be ‘cutting edge’ but is it really cutting edge if it appears in the newspaper?

Continuing our mental exercise, have they already succeeded in making someone, um, can’t really use the word ‘immortal’ because they are still capable of being killed or of dying in an accident. What would be an appropriate term? Could we call them ‘death resistant’?

Whether they’ve succeeded or not, does anyone doubt that somebody somewhere isn’t diligently mapping the path that leads to the ‘vanquishing of death’?

The only thing we know for sure is we’re twenty years closer to the first immortal walking among us since the ‘Jewish hippy kid’ checked out for parts unknown almost two thousand years ago.

Left to our imagination is who will be ‘left behind’ when this modern form of ‘eugenics’ takes on a life of its own…the overlords didn’t want to spend the money to educate the brats of their, ‘employees’. They will prove equally ‘resistant’ to footing the tab for ‘enhancing’ their own workforce. So what will become of those who can’t afford to ‘upgrade’ their, er, basic packages? Will they get what they need from the military? Which makes for another interesting puzzle, what if certain ‘improvements can’t be reversed AND it isn’t safe to let one so equipped to return to civilian life…what happens then?

Anyway, most of you know that I don’t think civilization will last long enough for any of this to become a problem.

Not only am I surprised to still be posting but I’ll be doubling surprised to still be posting this time next year.

Yeah, while this makes for a fun mental exercise, that’s about as far as it goes (with the possible exception of things they keep in cages in secret locations that nobody knows about except their creators.)

Things that make you go ‘hmmn…

Keep an open mind good citizen,

Thanks for letting me inside your head,


No comments:

Post a Comment