This is exactly what happens with UGA for selenocysteine. If you have a selenium deficiency, then the proper tRNA isn't synthesized and the ribosome stops translation like normal.
Incidentally, while the genetic code is pretty much universal, there are some variations. For example, in mitochondria, instead of functioning as a STOP codon, UGA encodes for tryptophan; instead of coding for isoleucine, AUA encodes for methionine; instead of coding for arginine, AGA and AGG function as STOP codons.
Evolution is all about kludges and supporting legacy operating systems. The genetic code is pretty much completely backwards compatible back to the most ancient prokaryote (though I'm not sure if it's completely the same in the archae kingdom) Nature also often ends up reusing code for completely unrelated purposes. And Nature never, ever throws away legacy code until she really, really has to. There are all sorts of non-working remnants from millions of years ago still floating around in our heterochromatin. And yet, for us humans at least, everything seems to fit in under 3 GB, including all the bloat and non-working code.
It depends on what you mean by "direct importance," I suppose. After all, it's quite possible to live a long and happy life without knowing any basic science whatsoever.
Still, while pyrrolysine may only be relevant to methane-producing bacteria, the similarly stop-codon encoded amino acid selenocysteine is incorporated into a couple of important enzymes like glutathione peroxidase (which keeps your red blood cells from lysing from oxidative damage) and 5'-deiodinase (which is important for regulating the activity of your thyroid hormone). Who knows what role the translation machinery plays in the etiology of diseases like hemolytic anemia, and hyper- or hypo-thyroidism?
The thing is, tRNA is only really specific for the first two bases in a codon. The third base can "wobble." For example, alanine can be represented in the genome by GCU, GCC, or GCA. This is because the anticodon (IGC) uses inosine to match the third base, and inosine can pair with uridine, cytidine, or adenosine. Only a couple of tRNAs require all three bases to match, like the tRNA carrying tryptophan.
The amino acid they discovered in 1986 is selenocysteine, which is also encoded for by a STOP codon (UGA in this case). Maybe there is an entire class of amino acids that are encoded in this manner, in between the 20 directly encoded amino acids and the multifarious post-translationally modified amino acids (e.g., hydroxyproline and hydroxylysine in collagen; gamma-carboxyglutamate in various clotting factors)
And you probably need more than just a STOP codon to incorporate pyrrolysine. With selenocysteine, you need enzymes to convert the serine residue on the tRNA to selenocysteine, an enzyme to activate the inorganic selenium, and a modified translation factor that recognizes this special case.
With regards to the light sensitivity problem, while I'm not sure how the chip actually interacts with neurons, if they've duplicated how the biological eye works, the photoreceptor's output would actually be inversely proportional to the amount of light hitting it. In complete darkness, rods (and cones) generate a so-called "dark current." (And unlike more typical neurons, they don't generate an all-or-nothing action potential) But as soon as only a single photon hits a single rhodopsin molecule, the signal transduction cascade amplifies the signal and decreases the dark current--seriously, the theoretical sensitivty of an individual photoreceptor is a single quantum of light. The thing is, though, the retina works nothing like a CCD--the brain does not read pixels. Before the entire signal even leaves the retina, it has already gone through two layers of integration. This is the reason why resolution is not straight-forward. By the time the signal has gotten to the primary visual cortex, the signal has already been translated into separate components depicting static orientation and direction of movement. So the real limitation is the practical resolution achievable that is somewhat hardwired by the genes that build the brain.
But back to the light sensitivity problem: In the biological eye, the magnitude of the dark current can be modulated by other factors like intracellular calcium concentration, which partially explains how the eye can adapt to different ranges of light intensity. (I.e., it partly explains why you're initially practically blind when you leave a movie theater but quickly readapt to outdoor light levels.) So if you made the artificial photoreceptor resistant to damage from, for example, sunlight, or even X-rays and gamma rays, to an extent, you could look at anything without ever worrying about frying your brain. But while the photoreceptive material can probably be easily changed to capture, for example, longer wavelengths for infrared or shorter wavelengths to see UV, x-rays, or maybe even electrons, the main problem would be that the signal would most likely be meaningless to the brain. At best, it would take a long adjustment period probably accompanied by nausea and vomiting before the brain could adapt to the signal, and then switching back to normal vision would require the same adjustment.
While many science fiction writers have already painted in detail various doomsday scenarios with regards to nanotech gone out of control, and while it's possible that once they perfect this specific technology, it may very well go out of control, I think the fear of direct infection from these viruses is alarmist. These viruses are specifically bacteriophages, and so far, no bacteriophage has been known to also infect eukaryotic cells. Admittedly, it's probably not impossible, but it's probably the least of our worries.
Since these viruses infect bacteria and not eukaryotic cells, you can more specifically refer to them as bacteriophages. But while I see your point regarding knee-jerk reactions to terms like "cloning" and "viruses," at the same time, people have been using viruses for non-malignant purposes for quite a long time already, specifically for the purpose of immunization. The first scientific demonstration of this was way back in 1796 (with the use of the cowpox virus to immunize people against smallpox.) Immunization has gotten so commonplace that I don't think that too many people worry about having to be purposefully infected by a live attenuated virus like measles or mumps or rubella in order to go to school or work at a hospital. While there will definitely be some phobic people out there, I think that the utilization of viruses has become so relatively mundane that it won't be as big a deal as with cloning or even the theory of evolution.
A lot of people are mentioning telomeres, but the reduction of telomere length is not the only possible determinant of aging. Some postulate the existence of actual clock genes that regulate the timing of intracellular processes, which have already been found in lower animals such as C. elegans.
But a huge determinant of cellular aging that isn't genetically encoded is simply physical damage due to normal cellular metabolism. Cells need energy, energy is generated by our mitochondria, mitochondria need oxygen, the presence of oxygen can generate reactive oxygen species which cause oxidative damage. (Lipofuscin granules--unmetabolizable oxidized debris that commonly accumulates within old cells--are evidence of such damage) While dividing cells can obviously repair themselves, some damage is simply irreversible. In the end, there are really only three ways for a cell to go: apoptosis, necrosis, or transformation into cancer.
The following does not really have any effect on your argument, but I just wanted to clarify some details:
Mitochondria may have been independent organisms once upon a time, but throughout the millions of years of evolution, essential genes have been removed from the mitochondrion's circular ring of DNA and integrated into the nucleus' DNA. So they aren't really standalone anymore, they are partially constructed through our cells protein synthesis machinery, and I don't think you can consider them "alien."
Mitochondria don't divide synchronously with our cells. As a vestige of their independent days, they replicate whenever they feel like it.
Actually, the modified children won't have all healthy mitochondria. Since it's currrently physically impossible to remove all the defective mitochondria from a host oocyte, the host mts will presumably live alongside the donor mts. This means that when the oocyte divides, the proportions of host mts to donor mts is very likely to vary from cell to cell. And considering that most mt defects continue to exist because they often give the defective mt some sort of replicative advantage, not to mention the fact that the defective host mts are probably better attuned to the host's nuclear DNA, and it's quite possible that the donor mts will still be overwhelmed. It's hard to say without knowing what the specific disorder is, though.
The current popular theory (endosymbiosis) is that a proto-eukaryotic organism consumed a prokaryote mitochondrion-like organism (i.e., capable of oxidative phosphorylation and all the other cellular respiratory mechanisms we've all come to know and love), and failed to destroy it. The mitochondrion-like organism prospered within the proto-eukaryote and continued to replicate as is its wont. The proto-eukaryote did much better natural-selection-wise with the extra ATP the mitochondrion-like organism was generating, and the rest is history.
But yeah, the theory rests on the fact that mitochondria, like bacteria, have a circular ring of DNA, have no organelles, their large ribosomal subunits are 70s (as opposed to 60s in eukaryotes) and their small ribosomal subunits are 30s (as opposed to 40s in eukaryotes), and they have roughly the same set of replicational, transcriptional, and translational machinery (which differs markedly from what eukaryotes use).
Other parts of the eukaryotic cell that may have once been prokaryotes are chloroplasts (only in plants) and peroxisomes.
Eliminating apoptosis completely would be a very bad idea. Apoptosis is just a way of hastening the inevitable, so that while an individual cell is dying, it doesn't affect the surrounding cells too much--it keeps the damage localized.
The stimuli that invoke apoptosis are usually factors that will kill the cell anyway--starvation, poisoning, radiation damage. Apoptosis is the cellular equivalent of euthanasia. Without it, the cell will still die anyway, except more slowly, and it will rupture and spew its contents to surrounding cells, possibly causing those cells to die as well. The process of aging and death of a multicellular organism is ultimately mediated by entropy, not genetics, so until we can figure out a way to repair the ultrastructure of a cell with nanotechnology, immortality is still a long way away.
What this discovery does allow us to do, however, is stop apoptosis in very specific situations (assuming that we have figured out all the cascade mechanisms, which is probably not likely at this stage). For example, in the aftermath of a heart attack, a stroke, or hypotensive shock, even if blood supply is restored, cells will still commit suicide because the apoptotic pathways have been activated. Experimentally, it has been shown that if you can block the stimuli that initiate apoptosis (such as the excess glutamate released in a stroke), then in these specific situations, the cells will probably do fine once the blood supply is restored.
So there are ways to shut off genes transiently--antisense RNA, competitive inhibitors of transcription factors, etc.--preventing much of the sequelae of these vascular events.
Still, shutting off apoptosis, even transiently, has the risk of inducing cancer. In stroke, for example, the excess glutamate triggers a cascade that generates factors that damage DNA. (These DNA-damaging factors are what directly activate the apoptotic pathways.)
So it's a choice: would you rather be paralyzed, or would you rather have a tumor? The odds are probably not even, so there would be a better choice, but ultimately, entropy can't be stopped, so achieving immortality would probably entail a lot of micromanagement.
While it's true that the effects of shortened telomeres were an initial concern when Dolly was first cloned, the article points out a more basic problem....
First off, so far, cloning involves taking out intact nuclei and putting them into an enucleated cell. We haven't gotten to the point where we can take naked DNA and stick it into an empty host nucleus.
This means that the proteins in the nucleus of the source cell will probably still have an effect on the development process, since, so far, there is no known technique that can remove all the proteins from the nucleus and still keep the structure of the nucleus intact. And it's already known that some of the proteins in an adult nucleus are different than what is found in the nucleus of a zygote.
The heart of the problem is this: a lot of embryological development is actually determined by elements in the cytoplasm, which must interact with elements within the nucleus (i.e., DNA plus proteins) What is speculated is that the different environment of the adult nucleus, particularly after the laboratory processing they undergo, causes all sorts of unpredictable interactions.
So in order to be more successful at cloning, we have to figure out how to reset the environment of the adult nucleus to match that of an embryonic nucleus.
But there is an even more basic problem than that: even natural fertilization and development is subject to a lot of random chance. Sometimes I think it's a wonder that life can reproduce at all. At least with humans, about 15% of recognized pregnancies end in spontaneous abortion and it is estimated that up to 50% of all conceptions end in spontaneous abortion, often before conception has been recognized. It's probably not too different for other mammals. So if scientists continue to get low yields, it shouldn't be that surprising. Even Nature doesn't get it right nearly half the time.
Oh, and just a little quibble about telomeres--a short sequence doesn't automatically and immediately doom a cell. A lot of cells your body have short telomeres and will never divide again, but they'll last almost your entire lifetime anyway (for example, almost all neurons)
What's happening to developing countries now isn't really the same as what happened during the Industrial Revolution, though. Europe and America weren't being economically colonized by other nations, i.e., money made in the U.S. typically stayed in the U.S (unless it was re-invested in foreign markets.) thereby generating tax revenue for the government, and allowing the government to subsidize necessary infrastructure like railroads and canals. Also, most of the economic policies of both Europe and America were extremely protectionist.
This is in stark contrast to what is happening to, say, the Philippines, which is a country that has probably been most true to the idea of laissez-faire capitalism of all Asian developing countries. The people who make the most money in Philippines are typically not Pilipino--therefore there are very, very few wealthy Pilipinos who can afford to invest. The government gets pretty much nothing from multinational corporations (unless you count the paltry bribes to corrupt officials), so there's no hope of improving infrastructure. The indigenous industries are barely subsistent, because the aforementioned elite would never dare to invest in them, and because the infrastructure is so bad. When you compare the progress of the Philippines to its nearest neighbors, I think it makes a good case against opening up trade barriers. It's ironic that you mention China to buttress you're argument for free trade--they probably have the most protectionist economic policies around! And it is probably the only reason they've managed to industrialize.
T and B lymphocytes make up only 20% of the white blood cell population. You're completely right about the splicing problem with these cells, and therefore, they're only interesting if you want to make a certain antibody. But the remaining 80% of white blood cells--granulocytes (mostly neutrophils) and monocytes--have all their DNA intact. Moreover, there is an available (though extremely small) population of less differentiated, less committed forms of all these cells (myelocyte-->granulocyte, monoblast-->monocyte, etc.) Though they aren't as pluripotent as the desired stem cells, they still have all their DNA intact, AND they can still divide.
I'm not saying that it's 100% impossible to make totipotent cells from differentiated cells. The thing is, I don't think the scientists involved are claiming that they can, either.
That's the problem. There is no difference from "normal" telomerase and "cancerous" telomerase. In fact, almost all cells in the human body stop making telomerase once they've differentiated.
The effects of aging that the original poster is talking about have almost nothing to do with DNA anyway. Even if all your DNA was free from catastrophic errors, there's almost no way for the body to fix non-cellular elements that have degenerated, like connective tissue. Or most of your eye.
The original poster isn't necessarily confused. He may not be talking about telomeres at all. Once the telomeres runs out, the cell just stops dividing. It doesn't necessarily die. The mechanism he is suggesting sounds more like the action of a tumor suppressor protein like p53--if it detects that the DNA is damaged beyond repair, it makes the cell commit suicide through apoptosis. But there are also other "clocks" in the cell--complex interactions of regulatory proteins--that scientists haven't completely elucidated yet. There is some indication that the Hayflick limit is actually due to interactions of glycoproteins on the surface membranes of adjacent cells and interactions with elements of the extracellular matrix rather than the telomere problem. So just adding telomerase and disabling p53--apart from being likely to cause cancer--still doesn't guarantee that the cell won't stop dividing and go apoptotic.
If they're just using blood cells to do this, I suspect they really aren't trying to cure Parkinson's or Alzheimer's or anything that requires generating CNS neurons. First of all, there are other scientists who have already claimed that they are able to retrodifferentiate neural crest derivative cells (specifically, cells from your adrenal gland) in order to cure Parkinson's--this would be pretty old news. Secondly, the article really only talks about curing leukemia, which seems completely feasible using only hematopoietic stem cells.
While regenerating stem cells from differentiated cells is a big deal--since it takes forever to isolate stem cells and grow them--it's nowhere near being able to generate a completely cloned human from a single random cell. There's an enormous difference between pluripotent stem cells and the totipotent cells found in a very early embryo.
While a pluripotent CFU can generate each and every single blood cell type, it can't generate neurons or striated muscle. While a pluripotent cell from the neural plate could theoretically generate any type of neuron and even cells that color your skin, the cells that help generate your teeth, and the cells in your adrenal glands, you wouldn't be able to make a liver or a pancreas from them. Only cells from before morulation have this kind of totipotency, and there's really no indication that they're actually causing cells to revert back to this level.
It's not an enormous leap to imagine being able to revert some differentiated cells to their stem cell derivatives. Obviously, erthryocytes can't since they've dumped all their DNA, and neither can lymphocytes, since they've spliced out a lot of theirs, but if other leukocytes keep their DNA intact, all it takes is removing certain regulatory proteins. Not a mean feat by far, but it's not magic either. And nowhere in the article do they claim they've retrodifferentiated completely differentiated NK cells, macrophages, or anything like that. For all we know, they could have just retrodifferentiated stem cells that are less pluripotent (like CFU-GM cells, which can only make granulocytes and macrophages) or even just the non-differentiated forms of RBCs or WBCs (For example, polychromatic erythroblasts, while normally committed to erythrocyte production, still have all their DNA and can still divide, so it wouldn't be too hard to get them to revert)
More obviously, they really haven't claimed that they've done anything about the telomere problem, which really puts a damper on the whole immortality idea. Sure, you could just add telomerase to the mix, but that's more likely to generate uncontrollably dividing cells than anything useful.
In other words, this is over-hyped. Sure, it's good news to people suffering from leukemia and other disorders of hematopoiesis, but if you need a new liver, don't get too excited.
I think just increasing the rate of mitosis is enough to cause problems. I imagine even a benign tumor in the eye would be bad.
Since uveal melanoma starts within such cells, there is a ready-made mechanism by which mobile phone radiation might help to initiate cancer, especially in people with a genetic predisposition to the condition.
This isn't a poor explanation at all. Excessive mitosis alone can lead to cancer, even if one isn't exposed to ionizing radiation that causes mutations. Mutation occurs at a given rate, even in normal individuals. It's up to the DNA replication error correction machinery to catch them.
Let's pick a random tumor suppressor protein, such as p53. It needs to be at a specific concentration in the cell to be effective at catching replication errors (which occur at a regular frequency even in normal individuals) Protein synthesis only occurs during G1 or G2 while DNA replication occurs in S phase and cell division occurs in M phase. Protein breakdown will continue at a relatively steady rate throughout the cycle, however. If the rate of DNA replication/cell division outstrips the rate at which p53 is synthesized (i.e., the length of time the cell spends in G1 and G2 phase decreases) and the breakdown rate stays constant, you've possibly effectively decreased the concentration of p53 in the cell.
But regardless of what the actual mechanism is, anything that can cause increased rates of mitosis (growth factors, signal transduction elements, whatever) can cause cancer because of the baseline error rate. Notice that the most common cancers occur in tissue with rapidly dividing cells such as skin and the colon. And it's not necessarily because they're more exposed to ionizing radiation.
While you're right in saying that it would take ionizing radiation to break the phosphate bonds between adjacent nucleotides, it does only take thermal energy to break the hydrogen bonds that link the base pairs. While you'd need to be at 95C to completely denature double stranded DNA, you'd only need much lower increases of temperature to just partially melt dsDNA enough. At physiological temperatures, dsDNA melts spontaneously all the time. This is why helicase can work, and that's why you need histones to stabilize dsDNA (and the hydrogen bonding between histones and DNA is much weaker than that between strands of DNA--much more easily broken by heat alone.)
But you're right in saying that a correlation is not necessarily meaningful. Without a mechanism, there's no need to panic yet. But if you take the scientific method to the extreme, nothing is ever true, you can only determine what is false.
I've seen quite a few posts mentioning this "ionizing radiation" thing. Shall I assume that it's only possible to cause uncontrolled cell division (e.g. Cancer) through damaging DNA directly, and not through indirect molecular mechanisms, such as causing RNA molecules to be built improperly? Is there a biologist out there who can confirm this, since it seems to be a common complaint about this article.
Nope, you don't have to damage DNA to cause uncontrollable mitosis. Increased production of growth factors and/or signal transduction elements can cause neoplasias as well (look what happens in the case of goiter, for example) While a neoplasia might not necessarily be cancerous, I'd imagine it would be rather problematic to have even a benign tumor in your eye.
Who knows what sort of effects even just a slight local temperature increase can cause. Perhaps it might stimulate cells to release autocrine growth factors. Perhaps it is enough to significantly speed up the delivery of growth factors via blood or the diffusion of signal transduction elements intracellularly. Of course, the key thing needed to cause a panic is to find the exact mechanism.
But I really can't see why thermal effects alone can't destabilize DNA or RNA. While the molecules themselves are stabilized by covalent bonds (albeit weakly) and very regular hydrogen bonds (in the case of dsDNA), both of which take a lot of energy to break, their interactions with other molecules, such as those responsible for DNA replication or RNA translation, are much more tenuous and don't necessarily need ionizing radiation to be broken.
Judging from the title of the paper, I think the experiment doesn't have much to do with conversion from L to D-amino acids.
Typically, helical chirality refers specifically to the "handedness" of macromolecules such as DNA and proteins. For example, DNA is normally in its "right-handed" B form, but it can also adopt a "left-handed" Z form. The handedness of a macromolecule is determined by the screw sense of its helix, Of course, these types of chiral compounds are also optically active.
Apparently, helical chirality can also apply to carbon chains with identifiable rotational conformations as well (rotational conformations such as gauche and eclipsed...best to refer to an O-chem textbook, because I don't remember them too well.)
In either case, it isn't too far fetched to imagine that copper atoms can cause changes in helical chirality.
But my question is: is this experiment about the helical chirality of poly-dialkyl-Met chains, or the helical chirality of a single dialkyl-Met residue?
While it's true that there is still a lot to learn with regards to how living organisms function, it isn't as if we didn't know anything before we could sequence. Much of the core functionality common to all living systems had been already elucidated early in the 20th century, even before we knew that nucleic acids were important. Just read a biochemistry textbook to see how far we've gotten without sequences of entire genomes. While there is a lot we can do with sequence info that we couldn't do before, I think most of our basic biological knowledge will still be derived from biochemical and molecular physiological experiments.
A better analogy for having the sequence info is like if Microsoft decided to release the source to Windows. Sure, we'd find out a lot of things we didn't know before, we'd find out specific implementations of algorithms, but it wouldn't necessarily tell us anything people didn't already know about operating systems in general. Obviously sequencing is not useless--it's definitely been one of the reasons we've been making so much progress lately--but it isn't the most crucial factor in figuring out how living systems work.
Check out the Berkeley Drosophila Genome Project, which also contributed to the sequence at http://www.fruitfly.org It's not just a private business venture.
It also needs more work--it's not exactly the entire genome yet.
At this time, ~92% of the genome is in contigs larger than 30kb, and ~78% in contigs greater than 100kb; most gaps are small (3kb or less) and due to genomic repeats, such as transposons.
If the entire sequence is 120Mb, that's a whole lot of pieces they still have to put together. Right now it's already probably good enough to do analysis of protein structure and a lot of the aspects of gene regulation, since they've gotten all the euchromatin, although we already know most of this stuff from the work of developmental biologists.
While the genes they found are interesting and it's great that they actually have sequence confirmation on them, we've probably suspected they were there for years now. Among the more interesting finds was the p53 analog, which controls apoptosis. and whose loss of function in humans is implicated in cancer. But this type of gene is expected to be found in all species that undergo regulative development. The SOD1 analog discovery was also interesting--in humans, this is one of the suspects for the cause of ALS. Its function is to clean up superoxides (perhaps lending credence to the theory that anti-oxidants will let you live longer), and so it wouldn't be that surprising to find something like it in all organisms that do aerobic respiration.
On another note, the progress with sequencing the Drosophila genome may not translate over to the human genome project, because working with Drosophila DNA has a huge advantage: genes are often present in multiple copies within a cell, due to polytene chromosomes. Instead of just having 1 set of double helices per chromosome, you could have 1024 sets or more.
Finally, I just wanted to quibble over the usage of the terms "map" and "sequence." Though they are similar, they are definitely not the same thing. The Drosophila genome could be said to have been mapped thirty or forty years ago, when Morgan did his work. (The units used to describe map distances are named after him) Mapping is the ordering of the genes--determining what chromosomes they're on and how far apart they are from one another. This is often sufficient to determine a lot of things, like inheritance patterns and rates of mutations. Sequencing is just getting the base pairs. A lot of the work will be to get the map and the eequence to match.
Are they preparing to make pig-human hybrids? They mentioned making the organs less susceptible to immunological rejection and also mentioned knocking out genes. This leads me to think that they might try and replace the pig's MHC alleles with their human analogs. This would be the perfect solution for prevention of rejection. (Of course, pig tissue isn't exactly like human tissue, so it wouldn't eliminate the problem completely, but it's a big step)
If this technique really works, the complications of rejection would decrease dramatically. You could really have custom organs made. Just let them get a copy of your HLA alleles, plug them into an adult pig genome, and inject it into an enucleated ovum, and you've got a backup system just waiting for you. It might even be better than human transplants with less than perfect HLA matches.
Of course, I'm sure there are a lot of people who will be quite uncomfortable with combining pig and human DNA. But if it works, isn't it more proof that all earth's creatures are made from the same stuff?
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Incidentally, while the genetic code is pretty much universal, there are some variations. For example, in mitochondria, instead of functioning as a STOP codon, UGA encodes for tryptophan; instead of coding for isoleucine, AUA encodes for methionine; instead of coding for arginine, AGA and AGG function as STOP codons.
Evolution is all about kludges and supporting legacy operating systems. The genetic code is pretty much completely backwards compatible back to the most ancient prokaryote (though I'm not sure if it's completely the same in the archae kingdom) Nature also often ends up reusing code for completely unrelated purposes. And Nature never, ever throws away legacy code until she really, really has to. There are all sorts of non-working remnants from millions of years ago still floating around in our heterochromatin. And yet, for us humans at least, everything seems to fit in under 3 GB, including all the bloat and non-working code.
Still, while pyrrolysine may only be relevant to methane-producing bacteria, the similarly stop-codon encoded amino acid selenocysteine is incorporated into a couple of important enzymes like glutathione peroxidase (which keeps your red blood cells from lysing from oxidative damage) and 5'-deiodinase (which is important for regulating the activity of your thyroid hormone). Who knows what role the translation machinery plays in the etiology of diseases like hemolytic anemia, and hyper- or hypo-thyroidism?
The thing is, tRNA is only really specific for the first two bases in a codon. The third base can "wobble." For example, alanine can be represented in the genome by GCU, GCC, or GCA. This is because the anticodon (IGC) uses inosine to match the third base, and inosine can pair with uridine, cytidine, or adenosine. Only a couple of tRNAs require all three bases to match, like the tRNA carrying tryptophan.
The amino acid they discovered in 1986 is selenocysteine, which is also encoded for by a STOP codon (UGA in this case). Maybe there is an entire class of amino acids that are encoded in this manner, in between the 20 directly encoded amino acids and the multifarious post-translationally modified amino acids (e.g., hydroxyproline and hydroxylysine in collagen; gamma-carboxyglutamate in various clotting factors)
And you probably need more than just a STOP codon to incorporate pyrrolysine. With selenocysteine, you need enzymes to convert the serine residue on the tRNA to selenocysteine, an enzyme to activate the inorganic selenium, and a modified translation factor that recognizes this special case.
But back to the light sensitivity problem: In the biological eye, the magnitude of the dark current can be modulated by other factors like intracellular calcium concentration, which partially explains how the eye can adapt to different ranges of light intensity. (I.e., it partly explains why you're initially practically blind when you leave a movie theater but quickly readapt to outdoor light levels.) So if you made the artificial photoreceptor resistant to damage from, for example, sunlight, or even X-rays and gamma rays, to an extent, you could look at anything without ever worrying about frying your brain. But while the photoreceptive material can probably be easily changed to capture, for example, longer wavelengths for infrared or shorter wavelengths to see UV, x-rays, or maybe even electrons, the main problem would be that the signal would most likely be meaningless to the brain. At best, it would take a long adjustment period probably accompanied by nausea and vomiting before the brain could adapt to the signal, and then switching back to normal vision would require the same adjustment.
While many science fiction writers have already painted in detail various doomsday scenarios with regards to nanotech gone out of control, and while it's possible that once they perfect this specific technology, it may very well go out of control, I think the fear of direct infection from these viruses is alarmist. These viruses are specifically bacteriophages, and so far, no bacteriophage has been known to also infect eukaryotic cells. Admittedly, it's probably not impossible, but it's probably the least of our worries.
Since these viruses infect bacteria and not eukaryotic cells, you can more specifically refer to them as bacteriophages. But while I see your point regarding knee-jerk reactions to terms like "cloning" and "viruses," at the same time, people have been using viruses for non-malignant purposes for quite a long time already, specifically for the purpose of immunization. The first scientific demonstration of this was way back in 1796 (with the use of the cowpox virus to immunize people against smallpox.) Immunization has gotten so commonplace that I don't think that too many people worry about having to be purposefully infected by a live attenuated virus like measles or mumps or rubella in order to go to school or work at a hospital. While there will definitely be some phobic people out there, I think that the utilization of viruses has become so relatively mundane that it won't be as big a deal as with cloning or even the theory of evolution.
A lot of people are mentioning telomeres, but the reduction of telomere length is not the only possible determinant of aging. Some postulate the existence of actual clock genes that regulate the timing of intracellular processes, which have already been found in lower animals such as C. elegans.
But a huge determinant of cellular aging that isn't genetically encoded is simply physical damage due to normal cellular metabolism. Cells need energy, energy is generated by our mitochondria, mitochondria need oxygen, the presence of oxygen can generate reactive oxygen species which cause oxidative damage. (Lipofuscin granules--unmetabolizable oxidized debris that commonly accumulates within old cells--are evidence of such damage) While dividing cells can obviously repair themselves, some damage is simply irreversible. In the end, there are really only three ways for a cell to go: apoptosis, necrosis, or transformation into cancer.
But yeah, the theory rests on the fact that mitochondria, like bacteria, have a circular ring of DNA, have no organelles, their large ribosomal subunits are 70s (as opposed to 60s in eukaryotes) and their small ribosomal subunits are 30s (as opposed to 40s in eukaryotes), and they have roughly the same set of replicational, transcriptional, and translational machinery (which differs markedly from what eukaryotes use).
Other parts of the eukaryotic cell that may have once been prokaryotes are chloroplasts (only in plants) and peroxisomes.
The stimuli that invoke apoptosis are usually factors that will kill the cell anyway--starvation, poisoning, radiation damage. Apoptosis is the cellular equivalent of euthanasia. Without it, the cell will still die anyway, except more slowly, and it will rupture and spew its contents to surrounding cells, possibly causing those cells to die as well. The process of aging and death of a multicellular organism is ultimately mediated by entropy, not genetics, so until we can figure out a way to repair the ultrastructure of a cell with nanotechnology, immortality is still a long way away.
What this discovery does allow us to do, however, is stop apoptosis in very specific situations (assuming that we have figured out all the cascade mechanisms, which is probably not likely at this stage). For example, in the aftermath of a heart attack, a stroke, or hypotensive shock, even if blood supply is restored, cells will still commit suicide because the apoptotic pathways have been activated. Experimentally, it has been shown that if you can block the stimuli that initiate apoptosis (such as the excess glutamate released in a stroke), then in these specific situations, the cells will probably do fine once the blood supply is restored.
So there are ways to shut off genes transiently--antisense RNA, competitive inhibitors of transcription factors, etc.--preventing much of the sequelae of these vascular events.
Still, shutting off apoptosis, even transiently, has the risk of inducing cancer. In stroke, for example, the excess glutamate triggers a cascade that generates factors that damage DNA. (These DNA-damaging factors are what directly activate the apoptotic pathways.)
So it's a choice: would you rather be paralyzed, or would you rather have a tumor? The odds are probably not even, so there would be a better choice, but ultimately, entropy can't be stopped, so achieving immortality would probably entail a lot of micromanagement.
First off, so far, cloning involves taking out intact nuclei and putting them into an enucleated cell. We haven't gotten to the point where we can take naked DNA and stick it into an empty host nucleus.
This means that the proteins in the nucleus of the source cell will probably still have an effect on the development process, since, so far, there is no known technique that can remove all the proteins from the nucleus and still keep the structure of the nucleus intact. And it's already known that some of the proteins in an adult nucleus are different than what is found in the nucleus of a zygote.
The heart of the problem is this: a lot of embryological development is actually determined by elements in the cytoplasm, which must interact with elements within the nucleus (i.e., DNA plus proteins) What is speculated is that the different environment of the adult nucleus, particularly after the laboratory processing they undergo, causes all sorts of unpredictable interactions.
So in order to be more successful at cloning, we have to figure out how to reset the environment of the adult nucleus to match that of an embryonic nucleus.
But there is an even more basic problem than that: even natural fertilization and development is subject to a lot of random chance. Sometimes I think it's a wonder that life can reproduce at all. At least with humans, about 15% of recognized pregnancies end in spontaneous abortion and it is estimated that up to 50% of all conceptions end in spontaneous abortion, often before conception has been recognized. It's probably not too different for other mammals. So if scientists continue to get low yields, it shouldn't be that surprising. Even Nature doesn't get it right nearly half the time.
Oh, and just a little quibble about telomeres--a short sequence doesn't automatically and immediately doom a cell. A lot of cells your body have short telomeres and will never divide again, but they'll last almost your entire lifetime anyway (for example, almost all neurons)
This is in stark contrast to what is happening to, say, the Philippines, which is a country that has probably been most true to the idea of laissez-faire capitalism of all Asian developing countries. The people who make the most money in Philippines are typically not Pilipino--therefore there are very, very few wealthy Pilipinos who can afford to invest. The government gets pretty much nothing from multinational corporations (unless you count the paltry bribes to corrupt officials), so there's no hope of improving infrastructure. The indigenous industries are barely subsistent, because the aforementioned elite would never dare to invest in them, and because the infrastructure is so bad. When you compare the progress of the Philippines to its nearest neighbors, I think it makes a good case against opening up trade barriers. It's ironic that you mention China to buttress you're argument for free trade--they probably have the most protectionist economic policies around! And it is probably the only reason they've managed to industrialize.
T and B lymphocytes make up only 20% of the white blood cell population. You're completely right about the splicing problem with these cells, and therefore, they're only interesting if you want to make a certain antibody. But the remaining 80% of white blood cells--granulocytes (mostly neutrophils) and monocytes--have all their DNA intact. Moreover, there is an available (though extremely small) population of less differentiated, less committed forms of all these cells (myelocyte-->granulocyte, monoblast-->monocyte, etc.) Though they aren't as pluripotent as the desired stem cells, they still have all their DNA intact, AND they can still divide.
I'm not saying that it's 100% impossible to make totipotent cells from differentiated cells. The thing is, I don't think the scientists involved are claiming that they can, either.
The effects of aging that the original poster is talking about have almost nothing to do with DNA anyway. Even if all your DNA was free from catastrophic errors, there's almost no way for the body to fix non-cellular elements that have degenerated, like connective tissue. Or most of your eye.
The original poster isn't necessarily confused. He may not be talking about telomeres at all. Once the telomeres runs out, the cell just stops dividing. It doesn't necessarily die. The mechanism he is suggesting sounds more like the action of a tumor suppressor protein like p53--if it detects that the DNA is damaged beyond repair, it makes the cell commit suicide through apoptosis. But there are also other "clocks" in the cell--complex interactions of regulatory proteins--that scientists haven't completely elucidated yet. There is some indication that the Hayflick limit is actually due to interactions of glycoproteins on the surface membranes of adjacent cells and interactions with elements of the extracellular matrix rather than the telomere problem. So just adding telomerase and disabling p53--apart from being likely to cause cancer--still doesn't guarantee that the cell won't stop dividing and go apoptotic.
While regenerating stem cells from differentiated cells is a big deal--since it takes forever to isolate stem cells and grow them--it's nowhere near being able to generate a completely cloned human from a single random cell. There's an enormous difference between pluripotent stem cells and the totipotent cells found in a very early embryo. While a pluripotent CFU can generate each and every single blood cell type, it can't generate neurons or striated muscle. While a pluripotent cell from the neural plate could theoretically generate any type of neuron and even cells that color your skin, the cells that help generate your teeth, and the cells in your adrenal glands, you wouldn't be able to make a liver or a pancreas from them. Only cells from before morulation have this kind of totipotency, and there's really no indication that they're actually causing cells to revert back to this level.
It's not an enormous leap to imagine being able to revert some differentiated cells to their stem cell derivatives. Obviously, erthryocytes can't since they've dumped all their DNA, and neither can lymphocytes, since they've spliced out a lot of theirs, but if other leukocytes keep their DNA intact, all it takes is removing certain regulatory proteins. Not a mean feat by far, but it's not magic either. And nowhere in the article do they claim they've retrodifferentiated completely differentiated NK cells, macrophages, or anything like that. For all we know, they could have just retrodifferentiated stem cells that are less pluripotent (like CFU-GM cells, which can only make granulocytes and macrophages) or even just the non-differentiated forms of RBCs or WBCs (For example, polychromatic erythroblasts, while normally committed to erythrocyte production, still have all their DNA and can still divide, so it wouldn't be too hard to get them to revert)
More obviously, they really haven't claimed that they've done anything about the telomere problem, which really puts a damper on the whole immortality idea. Sure, you could just add telomerase to the mix, but that's more likely to generate uncontrollably dividing cells than anything useful.
In other words, this is over-hyped. Sure, it's good news to people suffering from leukemia and other disorders of hematopoiesis, but if you need a new liver, don't get too excited.
Since uveal melanoma starts within such cells, there is a ready-made mechanism by which mobile phone radiation might help to initiate cancer, especially in people with a genetic predisposition to the condition.
This isn't a poor explanation at all. Excessive mitosis alone can lead to cancer, even if one isn't exposed to ionizing radiation that causes mutations. Mutation occurs at a given rate, even in normal individuals. It's up to the DNA replication error correction machinery to catch them.
Let's pick a random tumor suppressor protein, such as p53. It needs to be at a specific concentration in the cell to be effective at catching replication errors (which occur at a regular frequency even in normal individuals) Protein synthesis only occurs during G1 or G2 while DNA replication occurs in S phase and cell division occurs in M phase. Protein breakdown will continue at a relatively steady rate throughout the cycle, however. If the rate of DNA replication/cell division outstrips the rate at which p53 is synthesized (i.e., the length of time the cell spends in G1 and G2 phase decreases) and the breakdown rate stays constant, you've possibly effectively decreased the concentration of p53 in the cell.
But regardless of what the actual mechanism is, anything that can cause increased rates of mitosis (growth factors, signal transduction elements, whatever) can cause cancer because of the baseline error rate. Notice that the most common cancers occur in tissue with rapidly dividing cells such as skin and the colon. And it's not necessarily because they're more exposed to ionizing radiation.
While you're right in saying that it would take ionizing radiation to break the phosphate bonds between adjacent nucleotides, it does only take thermal energy to break the hydrogen bonds that link the base pairs. While you'd need to be at 95C to completely denature double stranded DNA, you'd only need much lower increases of temperature to just partially melt dsDNA enough. At physiological temperatures, dsDNA melts spontaneously all the time. This is why helicase can work, and that's why you need histones to stabilize dsDNA (and the hydrogen bonding between histones and DNA is much weaker than that between strands of DNA--much more easily broken by heat alone.)
But you're right in saying that a correlation is not necessarily meaningful. Without a mechanism, there's no need to panic yet. But if you take the scientific method to the extreme, nothing is ever true, you can only determine what is false.
Nope, you don't have to damage DNA to cause uncontrollable mitosis. Increased production of growth factors and/or signal transduction elements can cause neoplasias as well (look what happens in the case of goiter, for example) While a neoplasia might not necessarily be cancerous, I'd imagine it would be rather problematic to have even a benign tumor in your eye.
Who knows what sort of effects even just a slight local temperature increase can cause. Perhaps it might stimulate cells to release autocrine growth factors. Perhaps it is enough to significantly speed up the delivery of growth factors via blood or the diffusion of signal transduction elements intracellularly. Of course, the key thing needed to cause a panic is to find the exact mechanism.
But I really can't see why thermal effects alone can't destabilize DNA or RNA. While the molecules themselves are stabilized by covalent bonds (albeit weakly) and very regular hydrogen bonds (in the case of dsDNA), both of which take a lot of energy to break, their interactions with other molecules, such as those responsible for DNA replication or RNA translation, are much more tenuous and don't necessarily need ionizing radiation to be broken.
Typically, helical chirality refers specifically to the "handedness" of macromolecules such as DNA and proteins. For example, DNA is normally in its "right-handed" B form, but it can also adopt a "left-handed" Z form. The handedness of a macromolecule is determined by the screw sense of its helix, Of course, these types of chiral compounds are also optically active.
Apparently, helical chirality can also apply to carbon chains with identifiable rotational conformations as well (rotational conformations such as gauche and eclipsed...best to refer to an O-chem textbook, because I don't remember them too well.)
In either case, it isn't too far fetched to imagine that copper atoms can cause changes in helical chirality.
But my question is: is this experiment about the helical chirality of poly-dialkyl-Met chains, or the helical chirality of a single dialkyl-Met residue?
A better analogy for having the sequence info is like if Microsoft decided to release the source to Windows. Sure, we'd find out a lot of things we didn't know before, we'd find out specific implementations of algorithms, but it wouldn't necessarily tell us anything people didn't already know about operating systems in general. Obviously sequencing is not useless--it's definitely been one of the reasons we've been making so much progress lately--but it isn't the most crucial factor in figuring out how living systems work.
It also needs more work--it's not exactly the entire genome yet.
At this time, ~92% of the genome is in contigs larger than 30kb, and ~78% in contigs greater than 100kb; most gaps are small (3kb or less) and due to genomic repeats, such as transposons.
If the entire sequence is 120Mb, that's a whole lot of pieces they still have to put together. Right now it's already probably good enough to do analysis of protein structure and a lot of the aspects of gene regulation, since they've gotten all the euchromatin, although we already know most of this stuff from the work of developmental biologists.
While the genes they found are interesting and it's great that they actually have sequence confirmation on them, we've probably suspected they were there for years now. Among the more interesting finds was the p53 analog, which controls apoptosis. and whose loss of function in humans is implicated in cancer. But this type of gene is expected to be found in all species that undergo regulative development. The SOD1 analog discovery was also interesting--in humans, this is one of the suspects for the cause of ALS. Its function is to clean up superoxides (perhaps lending credence to the theory that anti-oxidants will let you live longer), and so it wouldn't be that surprising to find something like it in all organisms that do aerobic respiration.
On another note, the progress with sequencing the Drosophila genome may not translate over to the human genome project, because working with Drosophila DNA has a huge advantage: genes are often present in multiple copies within a cell, due to polytene chromosomes. Instead of just having 1 set of double helices per chromosome, you could have 1024 sets or more.
Finally, I just wanted to quibble over the usage of the terms "map" and "sequence." Though they are similar, they are definitely not the same thing. The Drosophila genome could be said to have been mapped thirty or forty years ago, when Morgan did his work. (The units used to describe map distances are named after him) Mapping is the ordering of the genes--determining what chromosomes they're on and how far apart they are from one another. This is often sufficient to determine a lot of things, like inheritance patterns and rates of mutations. Sequencing is just getting the base pairs. A lot of the work will be to get the map and the eequence to match.
If this technique really works, the complications of rejection would decrease dramatically. You could really have custom organs made. Just let them get a copy of your HLA alleles, plug them into an adult pig genome, and inject it into an enucleated ovum, and you've got a backup system just waiting for you. It might even be better than human transplants with less than perfect HLA matches.
Of course, I'm sure there are a lot of people who will be quite uncomfortable with combining pig and human DNA. But if it works, isn't it more proof that all earth's creatures are made from the same stuff?