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Precision Gene Editing

Zonk posted more than 9 years ago | from the i'd-like-some-gills-please dept.

Biotech 128

mpthompson writes "NewScientist.com is reporting that scientists at Sangamo Biosciences have developed a method of editing DNA mutations with unprecedented precision without weaving in potentially harmful foreign genetic material. Different combinations of amino acids are designed to latch on and cut the DNA at exactly the place where the mutated gene lies. This triggers the body's natural repair process which corrects the gene where the DNA was cut. The technique will be used to target diseases caused by single-gene mutations such as combined immune deficiency (X-SCID) - or bubble boy disease - and sickle cell anaemia."

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I don't care what they say.. (-1, Troll)

Prophetic_Truth (822032) | more than 9 years ago | (#12182225)

Once you start minipulating genes you're acting as god. Short term good may come of it, but the potential to screw up is an inevitable human trait..If we screw up here, we screw up bad.

OT: Anyone else noticed slashdot's 'free day pass' where u watch an ad then you get a free day of slashdot subscription? The thinkgeek ad was pretty funny.

Re:I don't care what they say.. (1)

grasshoppa (657393) | more than 9 years ago | (#12182264)

I would say that's a bit paraniod, and possibly based on some educational time spent watching the sci-fi channel.

Science is full of ethical questions, bio-sciences especially. What we can do we will do ( as a race ), that's a proven fact. It's better to do what we will do in the open, in front of many eyes, instead of being done in a third world country for some wacked out group intent on bringing their own version of reality to pass.

Re:I don't care what they say.. (1, Informative)

Prophetic_Truth (822032) | more than 9 years ago | (#12182350)

I would say that's a bit paraniod, and possibly based on some educational time spent watching the sci-fi channel.

PFFFT!!! GIVE ME A BREAK! You want the truth!?

I predict the following Prophecy:

Years from now we will have enhanced ourselves to the point where our skulls grow large and our eyes turn black. We no longer need to speak with our tounges, rather our minds. We no longer use sex as a means to reproduce. We have geneticly engineered ourselves to do things even I, Prophetic Truth, can not invision. BUT THERE'S A FLAW! A horrible flaw which can not be fixed by our future selves. A flaw of such consiquence that it will wipe out our species.

The solution?

Time travel, anal probes, and sperm collection.

The Prophecy has already been fulfilled

Re:I don't care what they say.. (1)

Rei (128717) | more than 9 years ago | (#12182355)

While the gp was really just being flamebait, there is a significant element of danger in genetic engineering.

Example: biobricks are really advancing, and you can already get custom genes made for a price that anyone can afford. Lets say that biobricks advance to the point where it's relatively trivial to make a gene that produces proteins that create Sarin, for example (or perhaps a different nerve agent with a longer life). You insert the gene into a common strain of phytoplankton found all over the globe, along with another gene to help give it a competitive advantage against its wild relatives. You then release it into the ocean (preferably in multiple points to speed up the process), and wait. The discovery of the source of the gas would likely be too late; almost everything with a nervous system would end up dead as the wind carries the gas across continents. A bioengineered apocalypse, in short, produced by someone with a bit of bioengineering knowledge and a couple thousand dollars investment.

Re:I don't care what they say.. (1)

John Seminal (698722) | more than 9 years ago | (#12182430)

Science is full of ethical questions, bio-sciences especially. What we can do we will do ( as a race ), that's a proven fact. It's better to do what we will do in the open, in front of many eyes, instead of being done in a third world country for some wacked out group intent on bringing their own version of reality to pass.

Just lable the experiments as labratories making weapons of mass destruction. LOL. Bomb. Invade. Elect pro-western government. Move on to next country.

But seriously. With genetic engineering, do you think that a third world country will work on curing cancer when they can work on building roads or opening hospitals?

The true threat is some western scientists move shop to a third world country. But we can track them down and arrest them for violating international law. Plus, the possibility of being punished in the third world country, and not the USA should be a huge detterant. We don't even need a fair trial.

Re:I don't care what they say.. (4, Insightful)

thanasakis (225405) | more than 9 years ago | (#12182266)

If sick people can get cured by something like this, we can't afford not to exploit it.

Let's just not forget that there is not such thing as evil knowledge. The way we use it makes good or evil.

Re:I don't care what they say.. (1)

jericho4.0 (565125) | more than 9 years ago | (#12182802)

Devil's Advocate; There must be a point at which it no longer makes sense to spend resources and risk opening Pandora's Box just to save sick people. People die.

GE is the technological revolution to shame them all, and will have massive impact on our society.

That said, I'm all for it, and will be first in line for gills.

Re:I don't care what they say.. (1)

flawedgeek (833708) | more than 9 years ago | (#12182276)

Sure, we could cause a ton of long-term problems. Keep in mind, though, that this sort of treatment is completely voluntary, and any doctor who doesn't go through the potential risks probably shouldn't be a doctor anyway. That, and the potential for fixing several of those nasty skeletons in the closet known as the human genome is motivation for quite a few, despite the risks.

Re:I don't care what they say.. (2)

Angry Toad (314562) | more than 9 years ago | (#12182277)

Errr...only if you affect the germ cells (sperm&eggs). Otherwise no altered trait can be passed along.

Re:I don't care what they say.. (1)

gr3g (119302) | more than 9 years ago | (#12182817)

because viruses never alter DNA

Re:I don't care what they say.. (2, Insightful)

EdwinBoyd (810701) | more than 9 years ago | (#12182284)

While I see where you are coming from, this process is no different than surgery on a fundamental level. Similar to removing a tumour or cist, it is a proceedure that if done properly can vastly improve the quality of life for the patient. According to the article after the 'cut' is made the body repairs the strand itself, so no insertion of new genes are required.

"It is the business of the future to be dangerous; (4, Interesting)

StefanJ (88986) | more than 9 years ago | (#12182287)

"and it is among the benefits of science that it equips the future for its duties."

-- Alfred North Whitehead, 1927

I only agree partially... (4, Insightful)

bennomatic (691188) | more than 9 years ago | (#12182294)

There are indeed dangers, but we've been doing this sort of thing for thousands of years; breeding of animals and plants is an old, old practice.

I know people who are geneticists, and who work in a lab where they are able to essentially make a mouse to order. You want one that grooms obsessively, here you go! Want one that glows in the dark? You got it. Just because they do it through genetic manipulation rather than breeding doesn't make it any more evil than other means.

What it does do is accelerate our ability to learn about life. Should we take things in measured steps? Absolutely! We should also have been more careful about asbestos, lead based paint, DDT, agent orange and more. But should we ignore these amazing advances? Absolutely not!

Re:I only agree partially... (1)

RealAlaskan (576404) | more than 9 years ago | (#12182527)

... we've been doing this sort of thing for thousands of years; breeding of animals and plants is an old, old practice.

... a lab where they are able to essentially make a mouse to order. You want one that grooms obsessively, here you go! Want one that glows in the dark?

I think there's a slight difference between selective breeding (which determine which of the genes already present in the species get expressed) and introducing new genes which were never before found in that species.

I see nothing wrong with these new techniques, just as I see nothing wrong with nuclear fusion, but I think your supporting argument is needlessly weak.

Re:I only agree partially... (1)

bennomatic (691188) | more than 9 years ago | (#12182945)

Yeah, I got that "my argument could be better" feeling in the pit of my stomache as I was writing, but I figured enough people would know what I meant. I'd thank you for the constructive criticism, but it was mostly just criticism.

So, thanks for the criticism :-)

That never stopped anybody... (3, Interesting)

nebaz (453974) | more than 9 years ago | (#12182298)

Before the first atom bomb was detonated, there were some scientists that thought that the nuclear reaction would spread and ignite the entire atmosphere. Despite their reservations, the tests were done anyway. Screwing up has never been a risk people considered worthy enough to stop a scientific experiment.

Re:That never stopped anybody... (1)

John Seminal (698722) | more than 9 years ago | (#12182329)

Before the first atom bomb was detonated, there were some scientists that thought that the nuclear reaction would spread and ignite the entire atmosphere. Despite their reservations, the tests were done anyway. Screwing up has never been a risk people considered worthy enough to stop a scientific experiment.

Yeah, that made me feel good about the USA. President Truman was told, we are doing the math, and we are 35% done, and so far we have not found a spike in the graph which indicates the nuclear explosion will continue until all mass is gone.

But then again, maybe Truman had alien data not available to the scientific community.

Re:That never stopped anybody... (1)

Solder Fumes (797270) | more than 9 years ago | (#12182331)

And the reason we went ahead and tested nukes? It was because those "scientists" could not come up with any better theories than crackpot ravings. They were ignored because their argument had no merit. If we held back everytime someone mentions eternal doom, we'd have never struck a flint into some tinder.

Re:That never stopped anybody... (1, Interesting)

Anonymous Coward | more than 9 years ago | (#12182360)

According to Bill Bryson's book (A Brief History of Everything, if I remember the title correctly), every young incoming physicist on the Manhattan project was assigned the problem of proving that the atmosphere wouldn't catch fire or that some new form of matter that would alter the earth would not be created...

Jack.

Re:That never stopped anybody... (1)

mpthompson (457482) | more than 9 years ago | (#12182557)

Well, that all good and fine, but I for one am just glad we don't live on planet Psychlo [battlefieldearth.com] where a nuclear bomb causes their entire atmosphere to catch on fire -- at least in the movie.

Re:I don't care what they say.. (2, Insightful)

iostream_dot_h (824999) | more than 9 years ago | (#12182348)

"short term good"? This has the potential to eradicate several crippling diseases and increase the quality of life of an innumerable number of people. You're going to have to give a better reason against gene therapy than "you're acting as god." You're personal religious opinions are not welcome in a diverse global arena, which is (or ought to be) tailored toward the pursuit of the greater good. You only serve to alienate those of us who may not subscribe to the notion that scientific progress runs counter to moral norms (a concept whose ontological coherence is debatable).

On a related note, this kind of attitude is precisely why scientific progress often stagnates. Irrational fear hinders societal good. Messing up a few times, as cold and calculating as this might sound, may be necessary in order to develop effective medicines and therapies and pinpoint options that do not work. The individuals who sign up for clinical trials are aware of the risks, and those who do should be applauded for their selfless contribution to the good of humanity.

Regardless of your personal beliefs, gene therapy is one of the most promising developments in medicine. It has the potential to revolutionize our perceptions of the human body.

Re:I don't care what they say.. (0)

Anonymous Coward | more than 9 years ago | (#12182661)

Maybe something you don't understand is that diseases, cancerous cells and the like are an evolution of life themselves. Something such as a cure for cancer is not only hypocritical in the sense that it is essentially killing a form of life, the fact is that it is an expression of natural population control.

Being stuck in a master-slave mentality of good and bad makes it remarkably simple for points of view like yours to seem reasonable when in fact they are intrinsically hypocritical. Just because something hurts or kills doesn't make it bad and just because something feels good or prolongs life doesn't make it good.

Re:I don't care what they say.. (1)

iostream_dot_h (824999) | more than 9 years ago | (#12183018)

"Just because something hurts or kills doesn't make it bad and just because something feels good or prolongs life doesn't make it good."

If you don't believe that human life is intrinsically valuable, and if you don't think that our cognizance and rationality are unique characteristics, then there is something fundamentally flawed about your point of view. Human life is uniquely valuable and we ought to make efforts to improve it. READ: It is not okay to acquiesce supinely while individuals needlessly die, especially when techniques are available to prevent such a thing from happening. Prolonging and improving human life is good. Ending it prematurely is bad. Simple? Sure. Deontologically sound? Definitely.

Re:I don't care what they say.. (1)

ianbean (525407) | more than 9 years ago | (#12183740)

I don't understand your arguement that cancer is a form of life. It is simply your own cells that have become defective. Curing yourself of cancer is like having your appendix removed (except that it's harder to achieve). It's not a form of life. Your immune system actively does this every day.

Cancer isn't an evolution of life either - life has spent billions of years evolving to a point where it is really good at preventing cancer. A car with smashed-in bumpers and its engine stuck on isn't a new type of car, it's just a damaged one.

Sure, cancer does contribute to population control, but if you're worried about that then maybe you should be campaigning against soap and fresh drinking water. Those make more of a difference than cancer treatments ever will.

Re:I don't care what they say.. (3, Insightful)

ciroknight (601098) | more than 9 years ago | (#12182378)

Forgive me for not believing in your esoteric views of this "God" character nobody has any proof of, but I feel genetic manipulation is going to be one of the few things that allow us (the human race) to continue existing.

As time goes on, we defeat simple diseases such as the bubonic plague, then upgrade to tougher ones like smallpox. We're now at the point where the only communicable diseases that are seriously fatal are biologically engineered bacteria, and viruses. On top of that, we've still got Cancer to worry about, which is kicking our asses.

While it may be cheaper to produce drugs for everyone alive and distribute them to everyone, no company in their right minds would do this. But if we could figure out genetically how to teach our immune systems to deal with cancer, and certain foreign invaders, we could save millions simply by changing our children's genes.

I think the biggest paranoia attributed to genetic engineering is the fear of change; just because we know how something works now, and we assume that it'll continue working the same way into the future, we give up the notion that we can change things for the better or for the worse. Yes, we are foulable creatures, but at the same time, we now know how to clean up our mistakes. It's far past time we take our fates into our own hands. Why use medicines that can screw up other things in our bodies when we can simply prevent the problem from occuring naturally?

Re:I don't care what they say.. (0)

Anonymous Coward | more than 9 years ago | (#12182444)

You exist in a dimension of space and time and you think its all coincidence..The universe has no purpose, its just here.

Re:I don't care what they say.. (0)

Anonymous Coward | more than 9 years ago | (#12182481)

I'm allowed to think whatever I want, and as there is no proof in any general direction, I simply don't think about it. Besides, if "God" didn't want us to manipulate our genes, it would stop us.

Re:I don't care what they say.. (0)

Anonymous Coward | more than 9 years ago | (#12183978)

No, I think all 20 billion years' worth of time and countless light years of space were created by a magical bearded guy just so you and I can exist on a little planet and persecute the people that don't believe in fairy tales.

Yeah, THAT makes sense.

Re:I don't care what they say.. (1)

Rei (128717) | more than 9 years ago | (#12182576)

Bubonic plague isn't "defeated"... FYI.

Re:I don't care what they say.. (1)

Frumious Wombat (845680) | more than 9 years ago | (#12183637)

Actually, we have a whole number of 'seriously fatal', excessively natural, diseases left. AIDS, Flu, Ebola, Malaria, and TB come to mind, plus the various drug-resistant streps, West Nile.

Genetic manipulation might allow us to finally treat diseases by some method other than mining other organisms for specialized toxins, then hoping the disease (which reproduces on the seconds to minutes time scale) doesn't become resistant too quickly.

Re:I don't care what they say.. (1)

mlyle (148697) | more than 9 years ago | (#12184305)

...the only communicable diseases that are seriously fatal are biologically engineered bacteria, and viruses.

As opposed to what, just-kidding-fatal? :)

Is X-SCID a DiVx format? (1)

FosterKanig (645454) | more than 9 years ago | (#12182229)

Just wondering.

Re:Is X-SCID a DiVx format? (3, Funny)

Tackhead (54550) | more than 9 years ago | (#12182314)

> NewScientist.com is reporting [ ...the ] technique will be used to target diseases caused by single-gene mutations such as combined immune deficiency (X-SCID) - or bubble boy disease - and sickle cell anaemia."
>
> Just wondering.

Funny you should ask. I just got this video from Paul Simon.

It's a turn-around jump shot
It's everybody jump start
It's every moderator throws a hero up the crackpipe
Singin' filk is magical and magical is pain, think of the boy in the plastic bubble
I'm a Slashbot with a baboon brain

(And I believe)
These are the days of lasers on a shark's head,
Lasers on a shark's head somewhere,
Staccato signals of constant information,
A loose affilliation of megabytes
And gigabytes and baby...

These are the days of miracle and wonder,
This is a long-distance boast,
The way the duplicate posts appear in slo-mo,
The way we go for first post.

The way we look to a Netcraft BSD troll,
That's dying like a server at NewSci,
These are the days of miracle and wonder
And don't cry baby, don't cry...

Re:Is X-SCID a DiVx format? (0)

Anonymous Coward | more than 9 years ago | (#12182375)

Just stay away from the brown X-SCID man.

day pass? (0, Offtopic)

master0ne (655374) | more than 9 years ago | (#12182230)

is it just me pr did slashdot add a "daypass" if you watch a commercial to see unreleased stories yet instead of subscribing?

Re:day pass? (0)

Anonymous Coward | more than 9 years ago | (#12182263)

Jeeze, did everyone get one of these? I thought I was special, kind of defeats the point if EVERYONE can see the article first doesn't it? That being said it's actually kind of cool, I never saw the point of subscribing, but I think I am now. $5 1000 articles, not too shabby.

Re:day pass? (0, Flamebait)

jericho4.0 (565125) | more than 9 years ago | (#12182831)

Give it up, Taco.

mmmyep (0)

Anonymous Coward | more than 9 years ago | (#12182267)

With adblock on it was just a matter of clicking a couple times, didn't see the ad. Now I see what I'm missing by not subscribing (hint: nothing).

Precision genetic engineering? (4, Interesting)

bobscealy (830639) | more than 9 years ago | (#12182255)

The article only mentions cutting the DNA and then "allowing the body's natural repair processes" to do the rest - it seems that this technique could also be useful in inserting genes at precise locations in DNA instead of letting viruses and bacteria insert genetic material wherever they please? I am no genetic engineer, can anyone comment?

Homologous Recombination (2, Interesting)

Seoulstriker (748895) | more than 9 years ago | (#12182320)

I have a feeling that this has to do with homologous recombination, where damage to a certain gene causes the chromosomes to auto-repair themselves by copying the target gene from the "good" chromosome. At least that's my take on why they would mention damaging the DNA to repair it.

Re:Homologous Recombination (1, Informative)

Anonymous Coward | more than 9 years ago | (#12182615)

Yes, it does have to do with homologous recombination. Creating a double strand break in the chromosomal DNA induces various DNA repair pathways including homologous recombination. The break can be healed by "copying" information off of the non-broken chromosome as you suggest.

If, however, you introduce a piece of "foriegn DNA" into the system at the same time that you make the chromosomal break, and that foreign DNA has homology to the DNA sequence flanking the chromosomal break, then the forien DNA can by recombined into the chromosome at the break point. Thus, one can insert any gene into a specific place on any chromosome (in theory).

Re:Precision genetic engineering? (1)

myc (105406) | more than 9 years ago | (#12182370)

you are completely correct. I fact, depending on how easy it is to design and make the custom zinc finger enzyme, I see this technology having far more use in research and engineering than in medicine. Many human diseases are recessive, which means both copies of a gene are defective, in which case getting a "normal" DNA template from which to repair from into a patient's cells is still a problem.

Re:Precision genetic engineering? (1)

nmb3000 (741169) | more than 9 years ago | (#12182523)

This triggers the body's natural repair process which corrects the gene where the DNA was cut.

No way. Anyone knows anything knows this will really result in a crazy mutation. Maybe they could play with the part of my genome that doesn't let me create fireballs in the palm of my hand and the body will "fix" it so I can?

Flying would be cool too.

Clarification (2, Interesting)

caryw (131578) | more than 9 years ago | (#12182260)

So this treatment actually alters the genetic code of a human? So any genetic disease would not get passed down to future generations? How is something like this administered? Our DNA is found in every cell of our body.
--
Fairfax Underground: Fairfax County message board and public records [fairfaxunderground.com]

Re:Clarification (1)

Taladar (717494) | more than 9 years ago | (#12182289)

Theoretically (without knowing anything about DNA,...) you could administer it in an early fetal state where the number of cells is still low. This wouldn't help the parent but could rid the child of the gene.

Re:Clarification (0)

Anonymous Coward | more than 9 years ago | (#12182313)

yeah, or it can be attached into modified viruses and spread to a localized area of the body, the virus infects the bad cells like it would normaly, only it spreads fixed DNA insted of its own harmful whatevers.

Re:Clarification (1)

YU Nicks NE Way (129084) | more than 9 years ago | (#12182813)

Unfortunately, no. The pole cells (the gamete progenitors) stop dividing at the blastocyst stage, which is reached at about the time of conception in humans.

Re:Clarification (1)

crypto55 (864220) | more than 9 years ago | (#12182400)

Maybe the scientists could create a virus that enacts the process at the cellular level to allow the change to take place throughout the body...

Re:Clarification (1)

mpthompson (457482) | more than 9 years ago | (#12182462)

The article states that "In the latest work, the gene was corrected in 18% of the cells treated, enough to finally make the method therapeutically viable." This would seem to actually alter the recipient cells' genetic code, but it is not completely effective over all the cells. Perhaps with time the technique will grow to the 80%, 90% or perhaps even 100% effective.

Re:Clarification (0)

Anonymous Coward | more than 9 years ago | (#12182521)

This works because you don't have to correct the mutation in ALL the cells in the body. The only cells that need to be fixed are the stem cells that will go on to produce the immune system. Pull out some marrow, isolate cells, fix, and then stick them back in.

Re:Clarification (2, Informative)

saytan (170239) | more than 9 years ago | (#12182566)

While I haven't read the article, I have heard a presentation on this from one of the researchers involved.

The old technology involves the use of a retrovirus containing the correct copy of the X chromosome gene involved. This copy inserts itself (nearly randomly) into the DNA. The problem with this was that you couldn't control the point of insertion, causing a whole new set of diseases.

The new technology involves repairing the endogenous gene sequence rather than inserting a good copy at another locus. By doing this, you get around the problems caused by random retroviral insertion. The key breakthrough in the new technology was the ability to make proteins that can cleave highly specific sequences. Researchers at Sangamo can custom make a protein to bind at only one place in a genome of 3 billion base pairs.

Both of these techniques work by taking out some stem cells from your body, transforming them, and placing them back in with your normal stem cells. This means that the DNA sequence of your germ cells, the cells that pass down your DNA to your children, is not changed.

Re:Clarification (3, Informative)

Fadeproof69 (874100) | more than 9 years ago | (#12182577)

In order to answer your question, i'm going to have to give a little background...

contrary to popular belief, 99.99% of the body's cells don't keep dividing. The somatic cells of the body are replenished by stem cells and progenitor cells which act as the main copy from which all the "backup" cells are made. These cells specialize into skin cells, blood cells, and possibly nerve cells. The only way to have a permanent effect with this treatment would be to fix the mutation in the stem cells/progenitor cells, so that future specialized cells will all have the fix incorporated.

To make this change heritable, you need to fix the mutation in the sperm or egg which is eventually used to create an embryo. Otherwise, the mutation will be passed on.

From what the article says, there's only an 18% transformation efficiency so of all of the cells treated (this would never be the entire human body, just the cells collected), only 18% will be fixed.

We are a long way off from doing the 100% effective gene therapy you see on Star Trek.

Re:Clarification (1)

jericho4.0 (565125) | more than 9 years ago | (#12182919)

For many diseases, you wouldn't need to get every cell in the body, only a propotion of the cells of a specific organ, like a bunch of bone marrow cells, for example.

The method used can vary by treatment, but in many cases, a virus is used.

Re:Clarification (1)

k98sven (324383) | more than 9 years ago | (#12183635)

So this treatment actually alters the genetic code of a human?

Yes it changes the genetic code. But it's not a treatment yet. It's a method which could be developed in a treatment. There's quite some difference between changing the DNA of a cell in a test-tube and doing it in someone's body. (In medical terms: in vitro versus in vivo)

So any genetic disease would not get passed down to future generations? How is something like this administered? Our DNA is found in every cell of our body.

Well, exactly. And you don't really want to try to change the DNA of every cell in the body, because you don't have to, you only need to change the DNA in some of the relevant cells. Mucking about with other cells (such as your sperm cells) would increase the risks.

If you read the article, what they're planning to do is take blood from the body, treat it, and reinject it.

(Although I think that sounds a bit strange; The disease is caused by faulty T-cells, which are in the blood. Shouldn't they be fixing the bone marrow cells, which create the T-cells? That's what these other treatments do. But this isn't my field.)

I'm Safe.. (4, Funny)

ackthpt (218170) | more than 9 years ago | (#12182279)

I've got PGGP - Pretty Good Gene Protection

they say diarrhea is hereditary, it runs in the jeans...

Re:I'm Safe.. (0)

Anonymous Coward | more than 9 years ago | (#12182341)

Watch out, when you die grave robbers might unencrypt you.

Re:I'm Safe.. (0)

Anonymous Coward | more than 9 years ago | (#12182569)

I've got PGGP - Pretty Good Gene Protection

Celibacy only prevents genes from being carried to the next generation.

Re:I'm Safe.. (1)

nmb3000 (741169) | more than 9 years ago | (#12182592)

What? No recursion? How about:

PGGP Generated Gene Protection.

Precise Gene Editing = Hex Editor (4, Interesting)

Proudrooster (580120) | more than 9 years ago | (#12182338)

Great, now the gene splicers have the equivalent of a hex editor, but still have no clue what they are editing. It's like hacking binary code out of one program and inserting into another program and somehow getting it to work.

Until we have a better handle on Gene Expression [wikipedia.org] and how to actually interpret the genetic code we should proceed cautiously.

To quote Dr. J. Craig Venter, Time's Scientist of the year (2000).

"We know far less than one per cent of what will be known about biology, human physiology, and medicine.
My view of biology is 'We dont know shit.' "


If any am being overcautious or am ill-informed please feel free to correct me. I try to live by the motto, "Just because we can do something, doesn't mean we should." This applies to System Administration as much as it does to gene-hacking.

In the case of specific genetic diseases (2, Informative)

MichaelPenne (605299) | more than 9 years ago | (#12182414)

like the 'bubble boy' defect mentioned in the article, we often know the specific bit of code that causes the problem.

"IL-7 signalling pathway

Most cases of SCID are derived from mutations in the c chain in the receptors for interleukins IL-2, IL-4, IL-7, IL-9 and IL-15. These interleukins and their receptors form part of the IL-7 signalling pathway.

The IL-2 receptor (IL-2R) gene is located on the X chromosome and mutation of this gene causes X-linked SCID.

Janus kinase-3 (JAK3) is an enzyme that mediates transduction of the c signal. Mutation of its gene also causes SCID."

http://en.wikipedia.org/wiki/Severe_combined_immun odeficiency [wikipedia.org]

Re:In the case of specific genetic diseases (2, Interesting)

Proudrooster (580120) | more than 9 years ago | (#12182554)

In certain isolated cases this has found to be true, but Dr. Richard Strohman, from UC Berkley wrote this.

"Genes exist in networks, interactive networks which have a logic of their own. The [gene] technology point of view does not deal with these networks. It simply addresses genes in isolation. But genes do not exist in isolation. And the fact that the [biotech] industry folks don't deal with these networks is what makes their science incomplete and dangerous."
Dr. Richard Strohman, Professor Emeritus of Molecular and Cell Biology at University of California, Berkeley. From his article "Crisis position". [EL]


So does this mean that until we understand the environmental interactions between, you won't fully understand how the organism will express its genes. This is similar to programming, since a program may run differently based on the environment in which it is run.

Sounds like Strohman is talking about (1)

MichaelPenne (605299) | more than 9 years ago | (#12182681)

germ line changes.

If a person has a terminal disease, somatic changes may or may not help, but they aren't likely to cause more damage than the disease.

And by the time they have a terminal (or even chronic) disease, you can get a pretty good idea how "the organism will express it's genes".

Treating disease in somatic cells is a much different issue from creating new lines of plants/animals/humans via changing germ line cells--at least in organisms that reproduce sexually.

Re:Precise Gene Editing = Hex Editor (3, Funny)

Anonymous Coward | more than 9 years ago | (#12182438)

Great, now the gene splicers have the equivalent of a hex editor, but still have no clue what they are editing.
Oh great, I can just imagine:

Razor 1911 brings you the penis extension hack.
Sequence cracked by: PhARAOh

GREETZ to MadKillas, Beowulf, Syxus, Toast, Trilithium.

Re:Precise Gene Editing = Hex Editor (2, Informative)

harvardian (140312) | more than 9 years ago | (#12182622)

Great, now the gene splicers have the equivalent of a hex editor, but still have no clue what they are editing. It's like hacking binary code out of one program and inserting into another program and somehow getting it to work.

This isn't entirely true. We can figure out where a gene starts in DNA, and we know how to read the DNA into a protein. We know that from the start point, DNA is broken up into 3's such that each set of three DNA bases code for one amino acid. To use the case of sickle cell anemia, the DNA sequence GAG is replaced by GTG. This causes a glutamine amino acid to be incorporated into the Hemoglobin beta chain instead of a valine (this can be predicted since we know the entire triplicate-to-amino acid dictionary). Partly because glutamine is a charged amino acid and valine isn't, this causes Hemoglobin with this mutated beta chain to clump together when deoxygenated -- hence the sickle cell phenotype.

So in this case it isn't true that we're hacking binary code. We're hacking a DNA code that we know enough about to fix simple point mutations like the one found in sickle cell anemia. As for other, more complicated, diseases, we are indeed still poking in the dark. But that doesn't mean progress isn't being made...

Precise Gene Editing = Patch Files (2, Informative)

cookie_cutter (533841) | more than 9 years ago | (#12183479)

Your right in that this doesn't give us the ability to do really novel gene manipulation.

But it does give us the ability to create the equivalent of patch files for bad/defective genes when a good/functional version of the gene is available.

There are many genetic diseases where the mistake in the DNA is well characterized, and it is very clear exactly what difference between the normal version of the gene and the defective version causes the disease, even if we don't have a full understanding of what the hell gene does; we just know to a high degree of certainty that a particular error causes a particular phenotype.

This new technology, if it lives up to the hype it's given here, could mean we can fix these kinds of diseases.

Re:Precise Gene Editing = Patch Files (1)

Proudrooster (580120) | more than 9 years ago | (#12183713)

Good Thread! I've learned a lot. To summarize, we could say that "everything we need to know about gene replacement therapy we have learned from Sesame street." when we learned the "One of these things is not like the other" [tripod.com] song :)

I just really bugs that I can look at hex and turn it back into op codes and get a general idea of what the code does, but we can't do the same with DNA. Maybe one day someone will be able to read DNA gene sequences like the morning newspaper.

Back in High School, I thought we would have a DNA construction kit by now, where you could hook it up to your computer and make custom organism with a limit on genome complexity e.g. (Banana Tomato Plant) or custom pets e.g. (Pet dog with tiger stripes). I believed we would have a complete understanding of DNA by Y2K, but then again I also believed that in the future we would have flying cars and computers would be able to program themselves with voice commands from the end users making programmers obsolete. Now I am wondering if we will figure it all out before my life is over.

Re:Precise Gene Editing = Hex Editor (1)

SCVirus (774240) | more than 9 years ago | (#12183705)

Uhuh... its not like experimentation has to start on humans... mice, small animals and blac... uh anyway, point being big step to super soldiers programmed to commit genocide!

Re:Precise Gene Editing = Hex Editor (1)

k98sven (324383) | more than 9 years ago | (#12183763)

Great, now the gene splicers have the equivalent of a hex editor, but still have no clue what they are editing.

They've had that for a long time. This is just a new one. Don't exaggerate the importance.

It's like hacking binary code out of one program and inserting into another program and somehow getting it to work.

A bit. But not quite as random as that. In this case, they know what the gene in question codes for a certain protein which acts as a receptor on T-cells. They know what the gene looks like in a healthy person. They know what it looks like in a person with the disease. They know that without this protein, the T-cell will die. They know that without T-cells the immune system won't work.

They don't know every last detail of the mechanism. But in this case; do they need to?

They know that replacing these faulty cells will cure the disease. This can be done through a bone-marrow transplant from a healthy person. (Donors for which are very hard to come by)

If any am being overcautious or am ill-informed please feel free to correct me. I try to live by the motto, "Just because we can do something, doesn't mean we should." This applies to System Administration as much as it does to gene-hacking.

Yes you're being overcautious, I think. You're missing the point that this disease already has been cured through other methods. You're missing that they know what the effects of changing this are. You're missing the point that these patients have a terrible quality of life and a very short life-expectancy. The alternative is literally letting them die.

You're missing the fact that they already are very cautious. They're not talking about using gene therapy to cure the common cold here. Gene therapy has so far only been used in cases like this, for very deadly diseases which we understand relatively well.

Re:Precise Gene Editing = Hex Editor (1)

Donny Smith (567043) | more than 9 years ago | (#12183985)

I just wanted to make this comment about hex editing (I thought to say that's like editing binary files with the vi editor) but I don't agree they shouldn't do it.

First, there are millions of ill people desperate for anything remotely promising. The alternative is suffering and death. Can it get any worse for them?

Secondly, initially they could perform this "patching" only on folks who agree to be sterilized (in order to limit impact on individual people until the technique is safe).

Thirdly, yes, it's not reliable, but look at the WAR3Z community - it's thriving and they're doing exactly the same thing - patching binaries based on trial and error. If individuals want to try out new things without harming others, let them give it a shot.

"Self-protection alone can justify either the states tampering with the liberty of the individual or any personal interference with another's freedom."
http://www.uark.edu/depts/comminfo/free speech/jsmi ll.html
(Crappy /. code screws up URLs. Can't that be fixed?)

Wow. Birth Defects No More (0)

Anonymous Coward | more than 9 years ago | (#12182342)

This means the son of the goatse.cx man will not be posing on the Internets.

Mutations... (3, Insightful)

John Seminal (698722) | more than 9 years ago | (#12182385)

That is how nature changes people, that is how humans evolved to what we are today. I dunno how smart it is messing with mother nature. So far, mother nature has been able to keep things going well for thousands and thousands of years. But for some human to say, I am not happy living to 80 years old, I want to live to 90 years old, that is a risky proposition considering they are not using standard medicine, but messing with DNA. Maybe what would have happened naturally now won't.

I think there is a natural equilibrium between nature and gene mutations. When the hand of man starts changing one side of the equation, can the consequences on the otherside be foreseen? For example, who is to say that some form of cancer today won't mutate to something 1,000 years from now that will save humanity from some enviormental change?

What if we get hit by an asteroid (1)

MichaelPenne (605299) | more than 9 years ago | (#12182614)

in 500 years, and between then and now millions of people suffer painful deaths to avoid changing something that might be helpful in the case of your hypothetical event?

Anyway, there is the whole somatic vs. germ line thing, if genetic engineering is limited to somatic cells, changes won't be passed on to children (unless we start reproducing via mitosis).

Re:Mutations... (1)

Fadeproof69 (874100) | more than 9 years ago | (#12182645)

Maybe we've evolved to a point where it's our destiny to control our future evolution?

If a form of cancer today will mutate into something that will save humanity in 1000 years, wouldn't it make sense to use our newfound knowledge and technology to keep people with these cancers alive longer so that they can pass these mutations on and allow them to mutate into something more interesting?

Re:Mutations... (2, Interesting)

BewireNomali (618969) | more than 9 years ago | (#12184386)

i think u bring up an interesting point. digital gene modeling.

programs similar to automata programs that currently run with simple sets of rules. each data set is a discrete genome. recombine over generations, tag all genomes that have disease preconditions and allow them to "evolve" that way.

it's interesting, because computing is ridiculously cheap and so is data storage. This can even be run as a distributed project. people volunteer their genomes anonymously and the entire simulation is run across the net.

the reason this is interesting is that we can see maybe a number of generations down the line... se how current trends in gene distribution occurred and possibly predict future trends.

Thats why have brains (1)

elucido (870205) | more than 9 years ago | (#12182820)

our brains allow us to control nature, not just exist in it. We can do whatever want, but we should be responsible when it comes to genetics because it puts our entire species at risk. If a person wants to design their genes let them, but there must be some rules and standards.

Re:Mutations... (1)

Joe Tie. (567096) | more than 9 years ago | (#12182957)

I dunno how smart it is messing with mother nature. Maybe what would have happened naturally now won't.

I know to some extent this is just complaining about syntax, but humans aren't magic. Anything we do is natural, and a part of our nature. We're no more violating some natural order by tinkering with our genes than the plant mentioned here a while back is by automatically changing its genes as a result of stress. If it works out well, great, it'll be selected for and in fact add to what can be selected for. In any case, just like some groups today won't accept blood transfusions I'm sure there'll be humans who won't take advantage of new genetics based medical technology. If in some sci-fi channel crazy situation we wind up taking ourselves out, fine, the amish, jehovahs witnesses and the like can just keep on going as they did before.

Re:Mutations... (2, Insightful)

Frumious Wombat (845680) | more than 9 years ago | (#12183576)

If you read Barbara McClintock's work and modern genetics, you'll see there are three events to worry about; mutations, exchanges with external organisms (virus, etc) and cross-overs. (genes exchanged during replication). Some people working with GA's have found that you don't need mutations at all, as cross-over events will give you all the variability you could want.

To answer your question, think of sickle-cell anemia. One copy of the gene, and you're resistant to malaria (but not immune, i.e. it simply kills you more slowly). Two copies, and you have sickle-cell anemia, and die early. The benefit of the gene outweighs the risk only as long as you don't have effective treatments for malaria. If you have good control of malaria, then it's better that you don't have that gene at all, as the net effect is deleterious.

We can't be sure of all of the ramifications, so we should make backups of anything we delete (CVS for your genes, so to speak), but in the end if we can short-circuit the process of better adapting ourselves to our environment, then we should do it.

A thousand years ago, genes that helped you resist smallpox and survive poorly fed winters were essential. Now, genes that coded for better DNA repair and reduced fat synthesis/uptake would be a better adaptation. We can wait for them to arise naturally (teenagers start keeling over from hardening of the arteries due to our first-world diet before they can reproduce), or we can engineer them, and introduce them into volunteers.

Re:Mutations... (1)

John Seminal (698722) | more than 9 years ago | (#12183672)

If you read Barbara McClintock's work and modern genetics, you'll see there are three events to worry about; mutations, exchanges with external organisms (virus, etc) and cross-overs. (genes exchanged during replication). Some people working with GA's have found that you don't need mutations at all, as cross-over events will give you all the variability you could want.

To answer your question, think of sickle-cell anemia. One copy of the gene, and you're resistant to malaria (but not immune, i.e. it simply kills you more slowly). Two copies, and you have sickle-cell anemia, and die early. The benefit of the gene outweighs the risk only as long as you don't have effective treatments for malaria. If you have good control of malaria, then it's better that you don't have that gene at all, as the net effect is deleterious.

We can't be sure of all of the ramifications, so we should make backups of anything we delete (CVS for your genes, so to speak), but in the end if we can short-circuit the process of better adapting ourselves to our environment, then we should do it.

A thousand years ago, genes that helped you resist smallpox and survive poorly fed winters were essential. Now, genes that coded for better DNA repair and reduced fat synthesis/uptake would be a better adaptation. We can wait for them to arise naturally (teenagers start keeling over from hardening of the arteries due to our first-world diet before they can reproduce), or we can engineer them, and introduce them into volunteers.

That is a good post. My point was, sometimes people think about the immediate and not the long term ramifications beyond our generation and the next. Not that our cave living ancestors probably gave much thought about us. But since we know nature works, I would say lets not mess with a good thing. Not for a few extra years of life, in our 80's or 90's, when we'll probably not be able to enjoy it. I am for medicine advances, all for research, but when it comes to changing DNA, I see a red flag. I think that even our brightest people are not able to consider all the potential ramifications.

It is like a game of chess, but the rules change. And we think we have a chance to change a rule to our benifit. But can even our best see the end game? Or are we just making a good guess, forseeing the next 4 or 5 or 6 moves?

More detail, less ZFN (1)

shift.red.avni (858445) | more than 9 years ago | (#12182398)

http://www.biologynews.net/archives/2005/04/05/res earchers_pioneer_new_gene_therapy_technique_using_ natural_repair_process.html

Bye Dorks (-1, Troll)

Anonymous Coward | more than 9 years ago | (#12182428)

Have fun on your computers tonight! Don't stay up too late playing your Doom 3 or whatever.

Not specific enough for safety (yet) (3, Informative)

G4from128k (686170) | more than 9 years ago | (#12182477)

TFA noted that the zinc fingers cue in on two sets of 6 base pairs to find the site that needs correction. Assuming randomness in the base-pair sequences, this 12 base-pair key will bind with approximately 1 out of every 16.8 million (actually 1 out of every 8.4 million due to complementarity of the base pairs). Given that the human genome has about 3.2 billion base pairs, this means that the modifier will match in 381 positions more or less.

Thus, this method will fix the error in one place and introduce an error in 380 other locations. The key needs more than 16 base pairs to be statistically assured of homing in on a unique mutation (depending on the statistics of DNA, it may need more or less).

Re:Not specific enough for safety (yet) (0)

Anonymous Coward | more than 9 years ago | (#12182580)

Don't have the specific details, but zinc fingers are modular to the point that you can build them to recognize sites in increments of 3. Most of the engineered proteins I know of use an 18 base pair site which is long enough to be unique in almost any organism's DNA.

Re:Not specific enough for safety (yet) (1, Informative)

Anonymous Coward | more than 9 years ago | (#12182778)

Upon careful reading of the paper, it seems from Fig. 1a, the Introduction, and the Materials and Methods, that two zinc fingers, each recognizing 12 bp are required for editing to work. The boolean sum of the recognition sequences of the two zinc fingers -- 24 bp in total -- is unique in the human genome.

with a PhD in Genetic engineering (4, Informative)

cinnamon colbert (732724) | more than 9 years ago | (#12182492)

I have not read the article, but repair processes can be "error prone". That is, the mechanisms cells use to repair DNA often involve high error rates.

The human genome is 3e9 BP long (roughly..not counting indels, the unsequenced centromeres, etc etc)

So the chemical process of identifying the one single mutated basepair has to have a chemical specificity of >>1e9, because there are >>1e6 cells that are exsposed. That is, lets say you feed the reagent to a person. Millions of cells, each with 1e9 bp, are expsosed. Say the process has an error rate of 1e10 - many, many cells will have incorrect repairs done
This is just like error rates in, say, reading data from a harddrive: the larger the file, the lower the error rte has to be

What /.ers may not appreciate is that typically, it is VERY, repeat VERY hard to get chemcial reaction specificity of anywhere close to 1e9 for reactions invovling DNA.

I will rtfa,

Re:with a PhD in Genetic engineering (3, Interesting)

Anonymous Coward | more than 9 years ago | (#12182628)

Yeah, but you have to ask yourself whether the elevated rate of DNA repair is significant compared to the constant repair going on due to standard ROS/RNS/other radical attacks.

And their current results of the 18% corrected rate, as they point out, is therapeutically effective.

Plus, their recognition system using zinc fingers may have a higher recognition rate for the targeted sequence, and the corrections are applied to only a small area of DNA - so the overall error rate of DNA replication/repair is spread out over the cells they are treating.

If I had a disease of the blood requiring gene therapy, I'd rather have this treatment than gene therapy using an adenoviral vector - that method is just asking for trouble with near random genomic insertion.

It's a clever idea - hope to see it developed further :)

When does the emacs module come out? (1)

Jeff DeMaagd (2015) | more than 9 years ago | (#12182524)

Really, emacs is a whole lot of stuff that just happens to have text editing functionality along with it, so why not genes?

having RTFA, (0)

cinnamon colbert (732724) | more than 9 years ago | (#12182531)

I note that the process involves removing blood from the body, running the process on cells purified from teh blood, and then reinjecting the cells back intothe patient.

I believe, but am not an expert in this field, that the simple process of removing cells from the body is in and of itself, highly mutagenic.

There is *no way* the cells could be checked before reinjection.

In any event, it is an interesting piece of science, but a LONG way from clinical practice - stay tuned for the update in 2020.

Re:having RTFA, (1)

saytan (170239) | more than 9 years ago | (#12182602)

The process of removing cells from the body isn't mutagenic. You are correct, however, in the assumption that it isn't ready for clinical practice quite yet, but it should be within a few years. At the moment, this only looks useful for single-gene traits caused by simple mutations (i.e. small deletions/insertions or single nucleotide polymorphisms, as opposed to major chromosomal rearrangements).

Re:having RTFA, (0)

Anonymous Coward | more than 9 years ago | (#12182714)

Are you sure removing cells is not mutagenic ? How would you verify this ? In mice, you could setup, say, in inactive GFP, or use a positive selection like an inactive G408 antibiotic maker, or HPRT or whatever, and inject balbc with akr cells, or whatever actually would work with out MHC rejection, and count how often it gets turned on, but you can't measure things in vivo in humans very well.

Re:having RTFA, (2, Informative)

lockholm (703003) | more than 9 years ago | (#12183350)

Actually, the simple process of removing blood from the body is not mutagenic - for example, think of blood transfusions, where blood is not only removed from the body, but frozen and stored.

Also, the large percentage of blood consisting of the red blood cells and platelets don't actually have any DNA in them to be mutated - these cells don't have nuclei.

Finally, in bone marrow transplants, one method of collecting the marrow cells to transplant is to hook the donor up to a machine through which their blood flows. In the machine, the stem cells (the cells that divide to produce all the elements of blood, including red blood cells and immune cells) are separated out, and these are the cells that are then transferred as the marrow transplant. You can find out more about this process here [health-alliance.com] . The objective with this treatment is to cure the cancer - so if simply removing the cells from the body causes cancer, it would be a very counter-productive treatment.

Good luck getting medical industry to fund this (2, Insightful)

Locke2005 (849178) | more than 9 years ago | (#12182550)

Pharmacorp executive: "Let's see now, we can sell them a one-time treatment that cures them for the rest of their lives, OR we can charge them $1000/month for drugs to maintain their current status for the rest of their lives... well, obviously we'll choose the method that is best for the patient's well being, our profits be damned! I mean, it's not like we have a board of directors that will sack us if our revenues don't increase every quarter!"

Yeah (1)

elucido (870205) | more than 9 years ago | (#12182881)

Thats why we don't depend on that industry. Buy your drugs in India, take a vacation and come back with your genes fixed.

The biggest danger of bubble boy disease... (1)

isny (681711) | more than 9 years ago | (#12182668)

[obscure Seinfeld reference] The Mooks.

Re:The biggest danger of bubble boy disease... (1)

slazar (527381) | more than 9 years ago | (#12183405)

DONALD: Ok, history. This is for the game. How ya doin' over there? Not too good!

GEORGE: All right BB. Let's just play... Who invaded Spain in the 8th century?

DONALD: That's a joke. The moors.

GEORGE: Oh, Noooo, I'm so sorry. It's the MOOPS. The correct answer is, The MOOPS.

DONALD: Moops? Let me see that. That's not Moops you jerk, it's Moors. It's a misprint.

GEORGE: I'm sorry the card says MOOPS.

DONALD: It doesn't matter. It's the MOORS. There's no MOOPS.

GEORGE: It's MOOPS.

DONALD: MOORS.

GEORGE: MOOPS,

DONALD: MOORS!

When are we going to see the treatments (0)

Anonymous Coward | more than 9 years ago | (#12182749)

I am getting real tired seeing all this great research, only to realize that treatments are the same tired treatments at the beginning of the century.

NONE OF THIS RESEARCH has changed people lives.

Stop with the fairy tales. People have not and will not get any new cures to any existing health issues.

#irc.trollta7k.com (-1, Offtopic)

Anonymous Coward | more than 9 years ago | (#12183219)

ThE chhosing

Isn't that how Umbrella does it? (0)

Anonymous Coward | more than 9 years ago | (#12183602)

Yikes!!!!

Gattaca!! (1)

tyman (831421) | more than 9 years ago | (#12184392)

My children can finally be bred as Valids!!!
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