An On/Off Switch for Genes 116
Jett wrote to us with a
report on some of the latest work being done in genetic theory. Scientists have made progress in being able to turn genes on and off at will, which is a critical step towards creating systems that will do what you want to them. This "toggle switch" can be triggered by either a specific chemical or a thermal rise. Nanotechnology is an area of convergence here as well - you can imagine the need for the ability to turn off some of your living nanites when unneeded.
This is all very cool and all, but ... (Score:1)
What I'm really waiting to come from all this genetic research is an off switch for small children who scream in the checkout line at the supermarket. Hell, I'd even settle for a simple 'mute' button. I mean, if genetics can't make that possible, then what's the point?
More info (Score:1)
Seems both the American and Chinese govternments have funded quite a large amount of research into these areas. What, pray tell, do the reds and americans have in store for the horrors of biotech....only time will tell.
-------- Charlie Benante
Re:Genes (Score:1)
I'll skip the personal slams and get to the heart of the matter. I have about 8 million years of evolution behind my position which states that this is the best system we have. Feel free to argue with mother nature. I don't think you'll get very far, however. Now, if you can get God on your side *that* would be a debate.
Re:Gilligan (Score:1)
NO CARRIER
Wow, 2084 ? (Score:1)
Just Imagine, some multinational companie opens up a chain of sperm banks in Europe/USA, and without knowing it the parents get an child that can be geneticly altered any time during it's lifespan.
The new person can then either be absolutely dependant on it's creator to suppress some gene functionality, or it could be "terminated" at any time by altering some food product this multinational company makes (Mc Donalds ?).
Why not create millions of people whoose life depends on drinking huge amount of Coka Cola and eating wast amounts of Cherios breakfast cereals ?
--
Why pay for drugs when you can get Linux for free ?
Useful? Could be... (Score:1)
Seriously. If this 'switch' is patched onto genes of a fetus before development, it could switch off any known genetic errors resulting in birth defects, deformities, etc. This could make genetic disorders rare. (save those disorders caused by UNknown errors.)
Plus, what about HIV? Sure, it's a virus...but if we can get bacteria to eat oil spills, why not shoot a boost to the immune system? Or hell, attach to the genes to release a known HIV inhibiter like AZT, and bam -- instant HIV progress slower.
(I'm not a doctor, and I make no claims as to the scientific validity of my comments. I just think they make sense.)
-- Give him Head? Be a Beacon?
Fruit flies? (Score:1)
Haven't they been doing this with genes in fruit flies for years?
TOYWAR [toywar.com]!!
Re:Genes (Score:1)
"The road to hell is paved with good intentions."
Please think long and hard about that one as it's got more truth to it that one might think.
Re:Look at our responses... (Score:1)
My intent is to provoke thought about the potential dangers that come with scientific advances, rather than to try to prevent the coming of those advances.
I guess we're pretty much in agreement about what needs to be done then. However, with anything related to genetics and humans the response is usually so strong and emotional that we are not really in that much danger of focusing only on the good.
I understand and appreciate this visceral reaction, and I think that "the public" is right to be skeptical. But, they/we have to take it a step further and not merely worry about whether this sort of thing is "against Nature" or "against God's will" - we/they have to determine what it is that we like about our society (or what it is that we would achieve ideally) and then set about controlling any new technologies. For some things that means don't use them at all (Biowarfare) and for others they should probably be used (giving people the option to do pre-pregnancy genetic testing). But, we've really got to increase public understanding of science. Otherwise people won't be informed, will know that their not informed and will thus be resentful, suspicious and unable to make logical choices.
The alternative? A mostly educated population choosing on the basis of informed rationality what they feel to be best. I look forward to it *g*.
Re:Genes (Score:1)
Re:Genetic variation (Score:1)
Actually, the lack of genetic variability in cheetahs isn't so much because they're "perfectly designed" as because they are on the verge of extinction-
I think you're misunderstanding me. I don't think that they're perfectly designed. I do think however that they are evolved. I was replying to a poster that seemed to feel that anything that had "evolved" was superior to that which had been designed. In fact, this is a premise of the Genetic Programming/Genetic Algorithm people - that an "evolutionary" process will necessarily be an optimizing process.
I'm very aware of the population bottleneck in cheetahs - a result of their evolution which is merely a contigent, stochastic process which responds to local environmental conditions.
I agree with most of what you've said but I think that you are a little confused with the following quote though:
-basically, as long as you have that much genetic variability you have "hybrid vigour".
Hybrid vigour is actually a term applied to the apparent increase in fitness of the offspring of a cross that involves two highly inbred parental lines. The extra variation resulting from this creates unpredictably (on the basis of extrapolating from h^2 calculations in the parental lines) fit phenotypes in the offspring.
Re:Genes (Score:1)
Really now, tampering with biological genes which have withstood thousands of years of evolution may destroy large sections of our world
Really now, I suspect that you are aware that not tampering with them might also be a problem.
I can only assume that you are trying to be provocative when you say :
make everybody intelligent. That's not such a bright idea either. With intelligence comes and increased desire to alter existing social structures. Get enough entropy stirred into the pool and the whole thing collapses into anarchy.
Why wouldn't altering existing social structures be a good thing? Are you happy with the present? If you really are serious about this then you should consider that while this attitude makes you merely smug and complacent it also makes a lot of people hungry, cold, nauseous, bitter, tortured and sad.
Really now, your facile discussion is at best irritating and at worst disgusting.
We simply are not at the point socially or otherwise to start tinkering with human genetics.
We already do quite a lot of tinkering: chorionic villi sampling and amniocentesis provide information on common genetic diseases to allow for the selective termination of foetuses at the choice of the parents. Also quite a lot of people are doing "selective breeding experiments" with human subjects! Yes, it's a procedure called sex!
Re:Why do we have to do this? (Score:1)
Do we really want to play around with our lives any longer? I mean, we've completely ruined our natural environment and wiped out countless species of animals. Do we want to wipe out ourselves as well?
I don't want to play around with our lives any longer. We've done that for too long, trusting to nature or to god. We have to understand how and why things happen. Then we can control them. You talk about an overpopulated earth stuffed with old people - well, letting nature take it's course is resulting in an overpopulated earth now. As for the old people, wouldn't it be possible to plan for a spectrum of people of different ages? With regard to people looking alike, aside from general tendencies to prefer certain proportions in the face and in waist-to-hip ratios (not overall fatness) there are diverse culturally determnined preferences.
The only thing you should be scared about is not understanding the technology and taking part in democratic decisions about it. Needless to say the former is a pre-requisite for the former.
A modern chastity belt (Score:1)
Re:A basic science use for this technology (Score:1)
My point was that if you classify things as prokaryotes vs eukaroytes, the easiet way to explain eukaroytes is as "basicly everything but bacteria", because for I think that is a good working defenttion for a non-biologist. "Basicly everything but bacteria" is a subset of life which includes plants and animals, amoung other things. If I told non-biologists that eukaroytes have nuclear membranes and prokaroytes don't, that wouldn't help much. If you don't know anything much about biology, would you know if yeast have nuclear membranes? (For those who don't know - obviously not the above poster - they do.) I was simply trying to provide a working defenition so that I could get on with post.
But since you have such a critical eye, I wonder if you have any comments about other ideas in the post. I'd be interested to hear.
Re:A basic science use for this technology (Score:1)
Re:Genetic switches have been known for a while (Score:1)
Nope. There called promoters and repressors. In some contexts, they are known as transcription factors. An operon is a set of genes which are expressed together. And the Lac operon was first explored in the 1950s by Jacob and Monod.
Re:Genetic switches have been known for a while (Score:1)
Like I said, since the 1950's. I was simply providing a correct date in response to the above post.
I dont see anything revolutionary in this "advancement" , we have known about it for years.
Well, the MSNBC article leaves it a little vague- I can't comment on the scientifc merit untill I get into lab tommorow and find a copy of Nature. But I think the point is that this is a promoter/repressor system which is easily turned on and off by an experimenter.
and the operon is NOT a set of genes expressed together , rather it is the regulatory and structural genes that regulate production of a certain protein
Were quibiling over scemantics, but I think in actuality, we are both half right. The genetics text infront of me (Griffith's et al., 1996) defines an operon as:
So I think we were both correct. The operon includes the set of genes expressed together (lac Z, Y and A) as well as the regulatory genes involved in that regulation (lac Pand O.)duh. old hat. (Score:1)
Because we do (Score:1)
Because it could save MY life, that's why. I have Crohn's Disease [ccfa.org]. I've had 4 surgeries in the past 2 1/2 years. I take medicine every single day for stabbing, throbbing pain in my gut. I hurt every time I have to go to the bathroom, or walk around for a while, or even just sitting in a chair. I've lost about a foot of intestines, and stand to lose more. Sooner or later, there won't be any more to take out. After one surgery, my bowel perforated, spilling the contents into my abdominal cavity, giving me septicemia (blood poisoning) and nearly killing me. I spent 4 months of hell recovering from that.
Why does any of this matter? I'm currently on Remicade [centocor.com] treatment, which is a monoclonal antibody. This medication, given intravenously a few times a year, has enormously improved my symptoms. The pain goes away, my appetite is better, I sleep better, and I feel like a normal person. If researchers had thought to themselves Why THE HELL would we want to change our genetic makeup? then the chances are that I'd either be in the hospital or so high on painkillers that I couldn't see straight. Remicade has changed the genetic makeup of my immune system, and I love it. It has made my life better and more enjoyable. I've dedicated my life to finding a cure for Crohn's Disease, and it will probably involve changing at least a part of the genome of the patient. If it gives them less pain and a better life, it's completely worth it, luddites notwithstanding.
Matt
Re:I am a Molecular Biologist... (Score:1)
I am a Molecular Biologist and I can tell you that this story is not in any way 'new' news.
In other words, MSNBC are lying. Not simplifying, lying. The MSNBC writer seems to be even more clueless than JonKatz, if that's possible.
Boolean Logic (Score:1)
Re:Genetic switches have been known for a while (Score:1)
more than that. (Score:1)
Think about how dinosaurs was wiped out. The great variations of genes protect the specie from other species, natural disasters, and all sorts of other things that might wipe out the entire specie.
Me think, Interfering with genes is a bad idea. Really, Really, bad.
At least we can thank Christians that this stupid idea of changing genes will get lots of resistance.
Re:Does this remind anyone of Gattica? (Score:1)
-----
Re:Useful? Could be... (Score:1)
Esperandi
Progress (Score:1)
Hopefully in the future we'll have computers powerful enough to simulate what a certain drug will do if it is ever combined with other drugs and things like that, but for right now we've got to live with risks or we'll end up standing still...
Esperandi
Re:A basic science use for this technology (Score:1)
Genetic variation (Score:1)
Poor argument indeed (Score:1)
I have about 8 million years of evolution behind my position which states that this is the best system we have. Feel free to argue with mother nature.
The logical conclusion of your argument is that we have somehow reached the pinnicle of evolution and that no more improvement can occur. This is nonsense - evolution is a continuous process and given another million years, we will have evolved into something better for whatever envionment we will find ourselves in. Using genetic engineering we can take shortcuts and condense a million years of evolution into a far shorter, directed process.
We certainly aren't the best system at all - I can think of a dozen things that could be done to improve the human race as a whole off the top of my head, and I'm sure you could too if you think about it.
Re:Useful? Could be... (Score:1)
Purpose of the on-off gene (Score:1)
Scenario 2: The diabetic recieves gene therapy for insulin under the control of a drug. The diabetic patient can take "time release" pills to deliver insulin steadily into her/his blood stream and therefore modulate the level of insulin in her/his blood by taking more or less pills. Allowing the patient to control the dosing of the insulin to their own personal preferences.
Better or worse?
Sure the company makes money selling the pills, does the consumer benefit? I think so! They can stop the therapy by not taking the pills.
This type of technology gives the decision to the consumer! I think it is a good development.
ps. by gene therapy I mean your blood (or muscle) cells are altered but your kids are still diabetic.
Re:The book on DNA Computing (Score:1)
Re:I am a Molecular Biologist... (Score:1)
Such is the annoyance the educated must endure.
-SaintAlex
Observe, reason, and experiment.
Re:More info on gene silencing (Score:1)
Gene silencing *is* also called antisense technology.
Reading A single book on the subject does not instantly make you an information source. You have to actually have an *extended* knowledge of the topic first (which you cannot get from simply one book).
Observe, reason, and experiment.
More info on gene silencing (Score:1)
"Another aspect of gene therapy is gene silencing, also called antisense technology. With this method, geneticists can inactivate a gene that may cause disease or be defective. When DNA replicates, RNA bonds to half of the split double helix, making a mold of sorts. The RNA (messenger RNA or mRNA) is then used to create an identical DNA strand. To silence a gene on a chromosome, scientists, therefore, simply make an RNA strand 15-20 bases in length complementary to the mRNA. The synthesized RNA will attach itself to the mRNA and prevent that portion of the mRNA from creating the gene on the duplicate DNA strand. This method is highly specific. Gene silencing is used to treat several viruses including AIDS, Herpes, Chicken Pox, and Hepatitis."
And in answer to all the people who ask why we would want to "play god", "because we can".
-SaintAlex
Observe, reason, and experiment.
Perhaps I'm just selfish but... (Score:1)
Re:Genetic variation: How? (Score:1)
NB - the 'germline' is a term describing the genes passed between generations, hence 'germline gene therapy', which is the editing of the genetic code to be passed from a parent to their offspring. Currently, and thankfully, the use of this in humans is taboo in most of the scientific community. 'Somatic' measures by contrast only affect the genes at work elsewhere in an individual, not the ones which will be passed on to their children.
Re:Genetic variation (Score:1)
Re:More info on gene silencing (Score:1)
Antisense technology is different to Gene Silencing. It can be used for gene silencing but also for other things.
Gene silencing can be performed through a number of different mechanisms. One of the more promising methods is ribozym (yes, without the e) technology which does work in vivo.
As for these genetic switches, the body comprises an extremely comples mechanism of feedback control. It operates on many many levels and one of the challenges molecular biology faces is how to cope with this. Data gathering is a huge task, microarray chips only address a tiny proportion of what we need to know in regard to how these mechanisms are controlled.
The current paper is interesting but like much of science can easily be dismissed by the 'knowledgeable but not expert' as 'standing on the shoulders of giants'.
As for evolution, with a small e it is a useful mathematical model for describing (no explaining) the relationships between different entities, with a large E it is a matter of pseudoscientific faith as to our origins.
Have a nice day.
Maybe /. should have some way of having expert moderators for such discussions. There are many good molecular biologists and bioinformaticians who cringe reading a lot of the inane drivel posted by the nonunderstanding.
Another cool feature would be kill lists so I don't have to read any anonymous posts...
Re:Horses (Score:1)
Really now, tampering with transportational systems which have withstood thousands of years of use may destroy large sections of our world. It's no joke - imagine if they "auto"-mated such tasks as laundry or cooking! Womenfolk could become idle and scholarly. With learning comes a desire to alter existing social structures. Enough disagreement and our fine society could collapse into anarchy.
How many "good ideas" are out there by well-intentioned people? How about we feed everybody good rich food and make humans with fast reflexes, strong muscles, and longevity? Sure.. that'll only spawn a deep chasm between the diet haves and the have-nots and might very well spark a war.
There are very serious and very dire decisions to be made with such technology. I hardly think such decisions belong in the hands of people making these decisions. We simply are not at the point socially or otherwise to start tinkering with human transportation. Understanding is one thing, modification is quite another!
OPEN SOURCE GENETICS (Score:1)
NEWS FLASH: GENETICIST LINKS ELVIS TO CHRIST!!
annaba, algeria, dr. christopher krustov, working in a hidden, underground laboratory, has presented the scientific community with shocking evidence which is sure to turn the world on its ear. dr. krustov, a world-renknowned geneticist, has found a genetic link between elvis presley and jesus christ.
"i always suspected a connection. it's rather quite obvious. jesus arose from the dead, elvis arose from the dead. people to this day report jesus sightings, people to this day report elvis sightings. jesus has millions of followers worldwide, elvis has millions of followers worldwide. jesus was the "king." elvis was the "king."
inspired by these keen observations, dr. krustov immersed himself in years of genetic research, his one goal to prove that elvis and jesus are, in fact, the same person!
"i was studying the shroud of turin and it suddenly dawned on me that there may be some significance to the crown of thorns. i managed to locate a patch of the same kind of thorns and gathered some for study. my tests showed that these thorns contain a chemical which has the effect of 'switching' genes!"
dr. krustov quickly compared genetic material harvested from a piece of elvis clothing with genetic material found on the shroud of turin.
"it turned out that the dna, with a few exceptions, was identical!"
the "few exceptions" turned out to be genes which had been "switched" by the poison thorns!
"this is a rather exciting time. after all of my study in genetics, i still find it amazing that just switching a few genes can turn a man who was a healer, prophet and 2000 years old into a fat, drug addicted rock star!"
thank you.
Does this remind anyone of Gattica? (Score:1)
Core dump (Score:1)
good and evil (Score:1)
Re:Useful? Could be... (Score:1)
People actually think about things like this, trying to get cells to express ribozymes that cleave their own chemokine receptors, and it could be useful one day, but I don't see this as the future of HIV therapy. Viral reservoirs (where the current antivirals can't reach) are the problem with HIV, not preventing infection of T-cells (which HAART triple cocktail therapy does a reasonable job of doing already).
Re:slight misrepresentation (Score:1)
Theoretically, none. Transcriptional regulation is dependent on the DNA sequence (called the promoter) upstream of the part of the gene that codes for the protein, so you can take whatever promoter you want and attach it to whatever gene you want.
Re:Wondering about prophylaxis (Score:1)
That's a really interesting idea, but I think it might be dangerous. I don't know how much is known about retrotransposons (transposable elements that use an RT to integrate the DNA copy of an RNA transcript back into genome), but some people think they have something to do with cell differentiation. Not to mention endogenous human retroviruses, about which very little is known. I think telomerase is also a form of RT, and you definitely wouldn't want to interfere with that. As far as RT inhibitors in HIV, there are non-nucleoside RT inhibitors used now in addition to AZT.
Luke
Re:More info (Score:1)
Apoptosis doesn't have much to do with aging, at least not in the way you're implying. Maybe you're thinking about telomeres? (confusing bandwagons is understandable)
This "toggle switch" paper doesn't say anything about shutting off apoptosis (or any cellular gene), and even if it did, you probably wouldn't want to "shut off" apoptosis since it probably plays important roles in your body. If you wanted to test your hypothesis about apoptosis, you could easily make caspase-3 knockout mice (transgenic mice lacking a gene responsible for apoptosis) and see if they live forever (if they weren't born dead). I'm sure the mice already exist. It would be a relatively simple experiment.
Luke
nanotech? (Score:1)
This and other reports I have read seem to suggest this, but I don't really see what this has to do with nanotechnology. If the paper discusses it, forgive me because I haven't had a chance to read it yet. But this just seems like an interesting way of controlling gene regulation. I guess the idea is you could transfect cells with something and use them as a delivery system? I see problems with this. I'm no expert in transcriptional regulation, but it's very different and a lot more complicated in eukaryotes than prokaryotes. Of course, regulating transcription of genes used in gene therapy will one day be critical (if we can ever figure out how to deliver the damn things). Luke
I remember reading about... (Score:1)
They were able to turn certian "toggle switches" in genes on/off.
The only problem was they were completely sure what the switches did.
A little AC who finaly got a nick.
Give me a break (Score:1)
Cloning a gene and putting it under IPTG-controlled expression in E. coli is now a second-year college molecular biology lab excercise. Putting it into higher organisms isn't anything new, or particularly exciting.
Trouble? (Score:1)
Organic computing (Score:1)
Re:More info (Score:1)
It sounds ridiculous, but understanding apoptosis (or now that I think about it, also necrosis: The sum of the morphological changes indicative of cell death and caused by the progressive degradative action of enzymes, it may affect groups of cells or part of a structure or an organ.) Now wouldn't immortality be great if we can simply turn off aging? Beware of the future ladies and gentlemen, we live in uncertain times.
-Jaffer
Tsk, tsk... (Score:2)
Oh wait.
Um, neither have I.
How are nanites any safer then bacteria? (Score:2)
Once we create nanites, presumably they will generate more nanites to cut down on cost, correct? And these nanites will produce more, right?
In any manufacturing process, errors will creep in. Usually, the damaged articles are thrown out. This would probably happen to the majority of nanites produced. But what if one error (mutation) is lucky enough to be more effective at replication? What if it's an error in it's "off" switch? Wouldn't we have the same possibility for a nanite plague as a bacterial one? And this time, with no known enemies, and unlimited raw materials...
Re:Why do we have to do this? (Score:2)
Because it may be the next step in our evolution.
Some science fiction writers have speculated that, when a species becomes intelligent enough, messing with its own wetware is the next logical step. After all, it was a natural process of evolution that led to the species becoming intelligent enough to understand genetics at all; why should subsequent deliberate manipulation of those genetics be any less natural?
And even if we take control of physical evolution, social evolution will carry on "naturally" much as it always has. Just a few hundred years ago, people thought slavery was fine, and that the Earth was flat and the center of the universe. We have evolved beyond it. We will evolve beyond this, as well.
Yes, the possibility fills me with unease, just as did global thermonuclear destruction. It may take a generation or two, but I suspect we'll learn to cope fairly well with this new power we've unleashed upon ourselves.
Schwab
Re:Genetic variation (Score:2)
Crush dun said:
Actually, the lack of genetic variability in cheetahs isn't so much because they're "perfectly designed" as because they are on the verge of extinction--populations of cheetahs have been reduced over the past few thousand years from millions in two species to a few thousand members who probably share something like fifty ancestors in common. (Cheetah populations, along with those of most other big cats, have crashed precipitously in the past 150-200 years or so.)
In fact, there is a fair amount of worry whether cheetahs DO have enough genetic variability to keep from going extinct. As noted, it's estimated that the ENTIRE cheetah population, worldwide, may well have less than fifty ancestors in common. (Fifty basal ancestors is considered the base minimum for a mammal species to perpetuate itself--basically, as long as you have that much genetic variability you have "hybrid vigour". This guarantees, roughly, that if something Really Bad happens to the species like a fatal disease epidemic or a bad summer drought, at least a few members will survive to live on and the entire species won't go extinct.) There is real concern that if some disease fatal to cheetahs were to become widespread that there is not enough genetic variability to save the species; for that matter, there is worry of an increased rate of birth defects in the cheetah population (you do get increased rates of both birth defects and genetic disorders when animals get too inbred--that's why there are laws against marrying first cousins in many states, and why areas with a large amount of inbreeding (like isolated Appalachian or island communities, or Ashkenazi Jews who were isolated in ghettos) tend to have rare genetic diseases that are not common in the general population).
If you want to see a really extreme idea of why not having enough genetic variability is a Bad Thing, look at Florida panthers (a subspecies of cougar that lives mostly in the Everglades). The total population has been reduced to around fifty or so individuals; many biologists do not think they have the genetic variability to survive as a subspecies any longer (especially since many of the panthers are also effected by "estrogen mimic" pesticides which have caused low sperm counts and feminisation in panthers). There is already evidence that inbreeding is affecting them negatively; many panthers are born with holes in their hearts and/or being born cryptorchid (one or no testicles descended), both of which are hereditary conditions in felids.
This is, incidentially, why extensive family trees are kept of animals being bred as part of the Species Survival Plan...they don't want them to get TOO inbred, and they want to maintain a good amount of genetic variability (especially for those animal species planned for reintroduction to the wild, like black-footed ferrets and California condors). This is also why typically if the number of animals in a species reaches less than 100 they tend to capture all the animals for breeding...
There IS one case where only around 150 individuals of a species survived and proceeded to repopulate the better part of a continent--that being American bison. (The herd had a great amount of genetic variability, which explains why bison aren't inbred to Hell and back like cheetahs or Florida panthers; the bison were INCREDIBLY lucky as a species to have the last herd have that much "hybrid vigour". The more religious of us might even say God/White Buffalo Calf Woman/Mom Nature/ must've been looking out for the bison ;)
Re:Useful? Could be... (Score:2)
Accipiter dun said:
I'd hope that they are careful about knowing which genes to turn off and on, then, as well as knowing which disorders this will work for and which it won't. ;)
As a minor aside--for the vast majority of genetic diseases, this isn't going to do anything at all--the vast majority tend to be either "bugs" in creating proteins or other essential body factors that cause the rough equivalent of a kernel panic or BSoD, or "stuttering" in genes in which a gene is repeated far too many times (basically becoming stuck in the genetic programming equivalent of an infinite loop).
For example, albinism is caused ultimately either by a gene that contains errors that cause the creation of tyrosine to "kernel panic", or by a gene that has errors that cause a buggy version of tyrosinase (the protein that converts tyrosine to melanin) to be produced that doesn't work. (I think all the computer programmers in the audience can appreciate that not everything that will compile properly in GCC will actually execute. This is what roughly happens with "tyrosinase-positive" albinism--the code for tyrosinase "compiles" properly (unlike in tyrosinase-negative albinism, where the code gives a "stop" because of an error) but it doesn't RUN right.) Both Huntington's chorea and Duchenne's muscular dystrophy are caused by repeats in genes that amplify across generations and add many extra copies of the gene (sometimes many, many extra copies--people with early-onset Huntington's can have as many as 500,000 extra copies of the gene).
Where "on-off" gene therapy may be useful is in disorders involving both "regulator" oncogenes and in some disorders where it's thought environmental factors trigger Something Really Bad happening to a gene.
For example, the oncogene "P-53"--if it's turned off or one is unlucky enough to get two bad copies of it--vastly increases one's chances of getting cancer. Most spontaneous cancers (even in folks who don't have bad copies of P-53--those who do have bad copies tend to show up with cancers very early in life, particularly retinoblastoma) also have P-53--which is thought to regulate cell division--turned off. This could be VERY useful in cancer therapies as a very specific form of gene therapy targeted directly at something that is specifically wonky in cancer cells (and in fact, some therapies for breast cancer are specifically taking that tack) to convert them to semi-normal cells.
This could also be really good for people with genetic tendencies towards autoimmune diseases or genetic diseases involving overproduction of enzymes. For example, one could turn off whatever gene leads to autoimmune reactions in people who develop rheumatoid arthritis or insulin-dependent diabetes (both of which are autoimmune diseases thought to be triggered by viruses; there is now speculation that motor neuron disease ("Lou Gehrig's" or "Stephen Hawking's" disease, depending on your generation) is caused either directly by a virus or is an autoimmune reaction to a picornavirus (if memory serves)). Also, in those cases of type I diabetes ("middle-age onset type I diabetes") in which the islet cells tend to be literally worn out [many, if not most people, with this form of diabetes tend to go into hypoglycemia, then diabetes--often severe enough to require insulin] it'd be REALLY nice to switch off that gene calling for the initial overproduction of insulin... :)
Unfortunately, I don't think it'll do much for Tay-Sachs, or any of the bad mitochondrial genetic diseases, or Prader-Willi, or maple-syrup urine disease, or any of the other really bad genetic diseases (mostly because these are the result of "programming bugs" that cause "fatal compile errors", or that cause "fatal runtime errors" in the proteins they code for, or that cause "infinite loop errors" that repeat a gene too many times, or which contain too many copies of a "library" which conflict with existing copies [chromosomal disorders--it's the repeats what cause most of them to be so bad as to be incompatible with life, and most of them besides Down's syndrome and the sex chromosomal trisomies/tetrasomies to be really bad for a kid in terms of longterm survival--those that survive tend to be mentally retarded and have all manner of health problems; you could also probably lump in disorders known to be affected on whether you inherit two copies of a gene from mom or dad in this [Angelman's Syndrome and Prader-Willi are like this--in one, two copies of the gene come from mom, the other, two copies of the gene come from dad]])...it MIGHT help in the cases where way too much of a protein is coded for, though. Perhaps the ultimate solution is that God really needs a debugger ;)
Re:Give me a break (Score:2)
Rhombic dun said:
Actually, if you count the genetic engineering Mum Nature's been doing for the past four billion or so years, a lot longer than that. ;)
Specifically, the "himalayan" or "pointed" genes that exist in most mammals (including, on rare occasion, humans) and most notably in Siamese cats are temperature-sensitive genes--specifically, there is a "bug" in the tyrosinase gene that only activates it at low temperatures. (Siamese kitties are born albino white at birth, and grow dark on the cooler parts of their body. If a cool pad is held against a Siamese kitten when they're starting to change colour (around four to six weeks of age), it can leave them with a dark spot where the cool pad was until their next good shed. Conversely, if the kitty is kept warm all the time, the kitty stays white.)
Yes, the gene exists in humans too; temperature-sensitive albinism is known (if memory serves, it's considered a variant of tyrosinase- negative albinism), and the humans tend to be red-headed or darker on their head, have dark hair on their lower arms and legs, and white or very light hair everywhere else (yes, almost exactly like a Siamese cat, because it's the exact same gene that causes "pointing" in Siamese cats).
Re:Genetic variation (Score:2)
The strength of evolved systems (mainly biological, but you can see it most easily in genetic programming) is that the huge mess of largely unreadable information is far more robust and flexible than a straightforward human-coded version.
Like Cheetahs for example? A highly evolved species, so evolved in fact that they have one of the lowest known genetic variations. I think that you are assuming that evolution is synonymous with best, which in your mind is synonymous with varied and able to respond to a variety of situations.
I really don't buy the genetic programming argument at all. It might work well for problems that have not been studied well and hence the problems and parameters are unknown, but given a clearly defined problem I'll go for human design any time.
introoduce an evolved system to a slightly different problem or environment, even one it's never seen before, and it is far more likely to deal gracefully than a "programmed" system.
I know this is reductio ad absurdum but here goes for some examples to disprove this statement:
I think GP is interesting, potentially useful for suggesting strategies when we don't have a clue, or when we are optimizing in parameter spaces with unfeasibly large dimensionalities for standard statistical approaches to apply, but that's all. Engineered design rules!
Re:Genetic variation (Score:2)
This would only be a concern if they were introducing these promotors and repressors into the genes of germline cells,
No, if the phenotype of the population is altered uniformly through somatic DNA by this technology then there may be too little variation left to cope with novel environmental threats. What if it turns out that we all need appendices to cope with a (presently) rarely occuring bacteria and we've eliminated it from all of the F0 generation?
We get eliminated, we leave no offspring.
On the other hand, if we changed the germ-line then it would only(!) affect the next generation - of course this would ultimately mean extinction for the race - but what the hell! If we were that stupid we deserved it.
Genetic switches have been known for a while (Score:2)
The switches(promoters & repressors) are also called operons. Their existence and functions have been known since at least the mid 80s and possibly even earlier. The most well known system is the Lac operon in E. Coli which triggers the transcription and generation of a protein that allows the utilization of lactose when there is no glucose present and a sizable lactose concentration. It's been pretty well studied and understood for a while. Although the article doesn't mention, the researchers were probably able to reliably splice a gene into a system like this and probably did not create the operon from scratch.
Re:Useful? Could be... They're already there (Score:2)
Actually switches like this are are already present. They let developing embyros regulate their own growth so that things like a brain develop only after a skull has formed. More importantly they let cells in the embyro figure out where they are so that they can become the right sort of cells. Errors in these are responsible for a lot of birth defects.
Re:Genetic variation (Score:2)
If they were to introduce these into germline cells such that it altered the total gene pool, there would be significant potential for diseases taking advantage of these, depending on the specificity of the sequences they use for whatever they are using as their trigger for the particular "switch".
Mike
slight misrepresentation (Score:2)
I wonder what restrictions this puts on the content of the genes...
A basic science use for this technology (Score:2)
With such a complex system, doing basic biology is difficult. For example, if I want to study the role a specific protein plays in the development of an organism, I can mutate it and see what changes. But what if that kills the organism (say, a fruit fly) early in development? I will have no idea if that gene plays a role later in development. But lets say I can engineer a line of flies with this switch acting on the gene I want to study. I can keep that gene on early in development, but shut it off at later times, learning the role of that gene at various points.
I'm not talking about sticking this into people for any reason (I'll let other people continue to bicker about that.) Despite the narrow vision of MSNBC and other popular media reporting on stories like this, I'll bet that the major impact of this advance won't be on any direct human advance, but will be in all the basic research it helps fuel.
I'm scared, for your children... (Score:2)
Get a grip, take your head out of the sand, and check to see how much technology has done to improve your life already. If you don't believe so, you can always take a long vacation in the Sudan or the slums of India to see what a grand life without the dangers of progress is like.
Re:This is all very cool and all, but ... (Score:2)
... There was a point to this comment, but it has temporarily escaped the poster's mind.
(apologies to Douglas Adams)
--
Re:Look at our responses... (Score:2)
On the other hand, is this something we can afford to ignore, or put on a shelf until we're more "responsible"? My grandmother has diabetes; if someone finds the "off" switch for this (or any other) genetic disorder, do we tell her, "Sorry Grammy, we could just give this one shot and fix you up, but theres's a risk of people changing their hair color so you'll just have to stick to the insulin."
Just a thought...
A good book on the subject of genetic switches (Score:2)
Me too :-) (Score:2)
I think I know what the problem is: unless you are into a certain field, something like "scientists found now a way of switching genes on and off" sounds like a sensation, and "it seems that leptine plays an important role also in lizard metabolic regulation" does not - even though the first one is, roughly speaking, nothing but journalistic bullshit, and the second a real revelation.
In spite of my miserable English knowledge I keep submitting to slashdot articles from Nature science update [nature.com] and some other sites that are providing good scientific information. Unfortunatelly, they do not sound as interesting and enthusiastic as what you can read about biology in "XXN news for housewifes".
By the way, I work at ZMBH [uni-heidelberg.de], Bujard, who developed the tet-system (which seems to work quite fine in many applications) also works here.
Regards,
January
Re:Progress (Score:2)
Yep. But if people are actively thinking about the costs in advance, the costs are smaller. Out of sheer desire to be annoying, I will point out the Y2K bug. It is not exactly the sort of thing we are talking about, but it makes a good metaphor. The costs were apparent because people were looking for them, and they were paid in a different fashion by having thousands of programmers work long hours rather than a catastrophic event. Had people not had the dangers inherent with it brought up, we might have truly had the catastrophe so many people feared.
Hopefully in the future we'll have computers powerful enough to simulate what a certain drug will do if it is ever combined with other drugs and things like that, but for right now we've got to live with risks or we'll end up standing still...
I don't really mean to indicate that we shouldn't have advances because we cannot fully understand their repercussions. That would indeed be standing still. I would like to suggest that people focus on what repercussions they would like to avoid, and focus more on those. That makes it less likely that those problems will occur. I was reacting to the unbridled enthusiasm and speculation of the first responses I read. I like enthusiasm, but not one person had written any comment indicating that they had thought of the potential dangers, so I did.
The guy who invented refrigeration died doing it, would you rather he have lived and we never got it?
No. I would have preferred that he took longer to get it and didn't die. I really mean to advise caution, not cessation.
B. Elgin
Re:Look at our responses... (Score:2)
Half-arsed research into something that is not "life-threatening" and thus treated less carefully will cost more lives than the delay in getting out the diabetes cure that comes from increased detailed inspection of these advances.
B. Elgin
Look at our responses... (Score:2)
I cringe every time I hear about an advance like this, because I stop to think: "OK, how can this be misused." Genetic engineering is a touchy ground with me, because the potential good for humanity does not necessarily outweigh the potential harm. For every gene we create with imperfect knowledge, we permanently affect some portion of the species we are working on. This is why serious geneticists insist on attaching terminators to sterilize genetically engineered crops. We have no good idea of what they would do to the natural species in our ecosystem.
Playing with our genes can be even worse. People will buy things they really don't want if it is sold well, and we are treading down the path towards that being our very genes.
"The salesman said not to worry, I will only start poisoning myself if this and this and this happens. In that situation it will be good." But how thoroughly was this tested and how good is the understanding we have of the systems involved. "Ooops. We are issuing a recall on that gene because we found out seven years later that this other thing can turn it on and the person dies. Sorry."
Unfortunately, this is not as far-fetched a scenario as we might wish it was. The on and off switch for genes is wonderful progress, but what will it end up costing?
B. Elgin
Re:Look at our responses... (Score:2)
I don't really object to the science at all, I just worry about the side effects. The unfortunate factor is that a very large percentage of any society values dignity and freedom, but there is a smaller percentage that ignores it. Usually, these are people who have never been in any danger of losing either, and do not place much value on them as a result.
My intent is to provoke thought about the potential dangers that come with scientific advances, rather than to try to prevent the coming of those advances. Usually, the good brought by advances such as these can be amazing, but if people only focus on the good and do not actively guard against the bad, you get quite a bit of the bad, too.
B. Elgin
Sounds like a job for moderation! (Score:2)
Ideas:
Topic-specific karma: points granted for posts in a particular topic go to your topic-specific karma, perhaps yielding:
A posting bonus whenever posting in that topic,
Moderation and meta-moderation opportunities specific to the topic,
Due consideration to submissions on that topic,
Pre-publication editorial/review opportunities relating to that topic.
Other ideas:
Recruit more paid article posters and editors with topic expertise, now that Slashdot is awash in IPO cash
"Instant karma" (I'm sure you've never heard _that_ before) to some folks credentialled in a certain topic.
Moderation guidelines or choices such as "inaccurate" for topic-expert moderators (this one's getting a little dicier, and I'd hate to see "stupid" questions cost karma)
"Article alerts" that get emailed to those wanting them for a specific topic. This would allow those of us with lives to only hit Slashdot when something cool comes along, and would let informative comments be heard before the topic gets old.
Anyway, you get the drift: is there a way to highlight/ascertain/reward expertise? If well done, it could really boost the level of discussion.
Re:Genetic variation (Score:2)
Why do we have to do this? (Score:2)
Why? Why must we play god or whatever you think made us in the first place? My argument is simple. It's not complicated. I haven't included any statistics or quoted any scientists. I might sound ignorant, but I just want to rule that out. I'm not ignorant just because I have a simple argument.
Do we really want to play around with our lives any longer? I mean, we've completely ruined our natural environment and wiped out countless species of animals. Do we want to wipe out ourselves as well?
Why THE HELL would we want to change our genetic makeup?
Some of the arguments for this type of research are:
1) We could cure some types of congenital disease. But do we really want to? As cruel as it may sound, what would happen if everyone on Earth died of old age? The picture in my head is that our already over-populated planet will be unable to sustain the sheer amount of it's inhabitants. But neither me, nor you, nor anybody on this Earth knows.
2) We could use the research to improve our lives. Create a perfect human. Why on Earth would we want to do that? Could we imagine a planet where everyone looks beautiful. Or even worse, with cloning, alot of people look EXACTLY the same? Do we really know what we're messing with here. Human character and individuality would dissapear. The world would become a very boring place.
Forget I said all that. Forget that I'm trying to change people's minds about this nonsense. Just remember one thing. I'm scared. Scared for my children, for my grandchildren, my friends and family. That's all.
Changing skin colors. (Score:3)
Genes (Score:3)
Really now, tampering with biological genes which have withstood thousands of years of evolution may destroy large sections of our world. It's no joke - imagine if they "switched off" the gene that makes us violent. We'd be completely defenseless - we wouldn't respond to violence, and hence the few genetic mutants that emerged would quickly dominate. Oh joy. How about this - make everybody intelligent. That's not such a bright idea either. With intelligence comes and increased desire to alter existing social structures. Get enough entropy stirred into the pool and the whole thing collapses into anarchy.
How many "good ideas" are out there by well-intentioned people? How about we turn everybody into "super" humans with fast reflexes, strong muscles, and longevity? Sure.. that'll only spawn a deep chasm between the genetic haves and the have-nots and might very well spark a war.
There are very serious and very dire decisions to be made with such technology. I hardly think such decisions belong in the hands of people making these decisions. We simply are not at the point socially or otherwise to start tinkering with human genetics. Understanding is one thing, modification is quite another!
Gilligan (Score:3)
Subject: Gilligan Nanite Processor
Release Day: Jan 19, 2004
After a long period of secrecy TransMetaTag Corp. finally announced the new Gilligan processor.
The new revolutionary processor uses nanites as it's core, translating Itanium instructions on the fly through a process known as "Gene Morphing". The nanites reorder and translate the instructions by pushing electrons through the right Gates at amazing speed.
"It was a breakthrough in nanotechnology that made this new design possible", says Linus Torvald Jr., "without the ability to turn them off, we could have never achieved our amazingly low power requirements".
Hemos could not be reached for comment.
The book on DNA Computing (Score:3)
DNA Computing : New Computing Paradigms (Texts in Theoretical Computer Science)
by Gheorghe Paun, Grzegorz Rozenberg, Arto Salomaa, W. Brauer (Editor)
A few people emailed me asking about this book, I figure this is a good time to post it for all to see... its a very good book and after reading it you'll realize this is a really nifty thing for DNA-based computers.
Oh, and NO DNA knowledge is needed to read this book, I knew bothing going in, now I feel like I could do the stuff in my basement if I knew how to get DNA out of a living cell or how to synthesize it...
Esperandi
We need a rheostat, not a switch (Score:4)
However, it's not really correct to think of (most) genes as being "on" or "off"; they are transcribed at a variable level depending on the local concentrations of one or several promoter proteins. The analog networks formed from these elements exhibit a variety of interesting nonlinear behaviors (of which switching is just one example) which help ensure that, for example, your cells divide at a rate just fast enough to replace their dying neighbors and maybe grow your body a bit -- but no faster.
We need to perturb these networks in order to understand them, but knocking out a gene or overexpressing it 1000-fold is like using a nuclear blast to twiddle the current in a sensitive circuit. Our lack of fine control over gene induction is one reason that dissecting gene networks is so hard.
Of course, there are other problems: biological control happens at the RNA [1] and protein [2] levels, not just the gene transcription level. We've got considerably better tech [3] for observing gene transcription than for watching proteins, but it's the proteins (especially the ones that bind to transcriptional promoters) that do the real work. Also, our analytical toolkit for network identification works great for linear systems but isn't so hot in the presence of nonlinearities and feedback.
For more information on how to analyze biological networks, see e.g. the proceedings of the latest Pacific Symposium on Biocomputing at
http://www-smi.stanford.edu/projects/helix/psb-
[1] RNA levels can be controlled not just by tweaking the transcription rate but also through selectively degrading mRNA's and by alternative splicing-out of introns to produce different transcripts.
[2] Proteins can be translated from mRNA and later degraded at variable rates. More importantly for fast responses, they can turn each other on and off through kinase activity (e.g. by adding and removing phosphate groups from particular sites in the protein).
[3] The latest and greatest tech for measuring gene transcription is the cDNA or oligonucleotide microarray. For example, see the GeneChip at www.affymetrix.com. Please don't ask me how quantitatively reliable these methods are -- the answer would only depress you
Re:Look at our responses... (Score:4)
This occurs naturally (Score:4)
I suppose the breakthrough lies in the ability to synthesize a genetic switch in vitro. As sensors, they will be a lot less invasive than mechanical and electronic sensors. But their implementation still faces the same barriers common to all gene therapy: delivery systems and persistence. We have yet to perfect a method for stably integrating a synthetic chromosome into a eukaryotic cell, and transfection of small pieces of DNA is usually temporary because they will rarely integrate with the genome.
In terms of revolutionizing genetic engineering, if we do figure out how to insert such a switch into a pre-existing gene, we'll only be able to solve autosomal dominant disorders, and only the ones that are due to dominant negative effects, like some forms of osteogenesis imperfecta, where a bad copy ruins the good copy too. Other autosomal dominant disorders are due to haploinsufficiency, meaning that one good copy isn't enough for the job, so turning off the bad gene won't help. Autosomal recessive and sex-linked disorders cause problems because there are no good gene products, so turning off genes won't really help, and there isn't anything to turn on. In any case, if we were to understand such a gene well enough that we could confidently install a switch, it would just be easier to replace the bad gene with a good copy than inserting the switch.
It would be interesting to construct a computer from genetic switches, however. Such a switch wouldn't have to only represent 0 and 1.
I am a Molecular Biologist... (Score:5)
and I can tell you that this story is not in any way 'new' news. Maybe the nano blurb is a new idea for this technology, but the idea of turning on and off engineered genes at you're discretion is not.
The system they are referring to is known as a tetracycline responsive promoter. A commercially kits for this purpose are available here [clontech.com].
Having used the system, I can tell you it does not work very well. A better system is located here [invitrogen.com] and an even newer system here [invitrogen.com]. I rarely post here, but I have noticed that most of the pieces on biologically related topics that make it on /. are not well researched on the poster's part. When I think about it, the majority of news and pseudonews sites on the web and in the traditional media fail miserably when producing stories about science in general and particulary regarding biology.
Yo