...than for actually controlling your brain. One of the biggest obstacles for genetic engineering is how to get the DNA inside a cell. Electroporation is just one of several ways, and apparently they've refined the process. This will probably make it so that the pore size can be controlled, so that only certain molecules can get in, and it will probably minimize the damage to cell, too. (although I'd imagine sticking the chip inside in the first place would do a lot worse damage than shocking the cell.)
I suppose this is for all those people who are leery of using replication-incompetent retroviruses, which right now are much better at sending their payload to specific tissues in-vivo, but it's not entirely certain that they can't mutate and regain their replicative abilities.
I admit that I don't understand physics nearly as well as I understand molecular biology, but I don't think this theory of "quantum evolution" contradicts Darwin at all (for one thing, Darwin really never said anything about how mutations occur.) It might even have a place in the current model for mutagenesis (well, at least the model that I learned.)
Mutations are simply the result of alterations to DNA. DNA, like all molecules, rapidly interconverts between several energetically equivalent conformations. Specifically, the bases that comprise DNA can interconvert between imidine forms and amino forms. (And the base pairing rules change depending on which form the base adopts.) As long as nothing interacts with the base, it exists, in a sense, in an indeterminate state (This might serve as the mechanism for "sampling" mutations.) Only when the base interacts with another molecule, such as its base pair, does the base "crash out" of the "quantum foam" into one of those conformations. Whatever it is interacting with, whether a mutagen, an enzyme, or its base pair, actually forces it to adopt a conformation. (And vice-versa. Although in reality, I imagine that it still isn't really locked into one conformation, it's just that the probability of it existing in that conformation has increased, while the probability of it existing in the other conformations has decreased.)
It is because of base-pairing that mutations don't happen more often, but when DNA is replicating, or being transcribed, the bases can often be in an unpaired (and therefore indeterminate) state. When the base is again paired, it might have adopted the "mutated" conformation instead of the (normal) "wild-type" conformation. But even then, most mutations are still reversible because of the energy available in the system (manifested through repair enzymes and the concomitant hydrolysis of ATP)
So in a sense, every single base in every single cell in your body is rapidly fluctuating between a "wild-type" state and a "mutated" state. So every single moment, a sort of natural selection occurs in that the combinations of conformations that favor survival is selected for. But here is where "quantum evolution" might be flawed, if what the article seems to implying is true. The article seems to say that there is some novel principle that provides this selective pressure--some force that favors life. But I think the nature of this selective pressure is a lot simpler. I think it's just thermodynamics.
Whether or not a mutation persists depends on whether it is energetically favorable or not. Normally, the wild-type, particularly when it is interacting with its base pair, is energetically favored, but put in energy, like in the form of a gamma ray, and the mutant conformation can be favored. Of course, the mutation can always be repaired, but this too depends on the energy available in the cell. If the cell doesn't have a lot of ATP to spare, and the mutation doesn't kill it right then and there, it is likely that the mutation will persist.
This process is pretty much what directs evolution in single-celled organisms (which pretty much make up the majority of all life forms and whose history pretty much dominates all of evolution), and it works pretty much the same in multicellular organisms, except that only a small fraction of cells actually get to propagate mutations, and a lot of it gets covered up by sex anyways. Mutation isn't really an all-or-nothing event, but more a summation of probabilities, which don't actually get locked in until it's time for the mutation to be propagated. And all this applies to acellular DNA, too. Since we know that DNA can be synthesized abiotically from simple gases and lightning, and that the ability to replicate is a direct consequence of the structure of DNA, it isn't really that much of a leap to imagine the evolution of a nucleic acid into a single celled organism. It's really all just thermodynamics.
One might argue that thermodynamics actually favors the destruction of life (i.e., since disorder ever increases), and in a sense it's true since we all die, but luckily thermodynamics doesn't say anything about how fast something happens. Using the hydrolysis of proteins as an example: protein + H2O --> amino acids, which is exergonic, may seem to prove this even further, but this forgets to include the fact that in protein synthesis, ATP is hydrolyzed too, and this actually makes it thermodynamically favorable to make proteins. The reason life occurs is because thermodynamics says it can, and given enough time (namely, billions of years), anything that thermodynamics says can happen will, no matter how improbable you think it is. So evolution isn't really random at all, and you don't need to look farther than college chemistry to see why.
Why don't they just couple this with, say, glycolysis or the electron transport chain so they can regenerate NADH as much as they want? Couple these to photosynthesis, and you could cut CO2 emissions even further. Use the enzymes out of some archaebacteria, and you could filter out nitrogen or sulfur byproducts as well.
Here's a theoretical pathway (the real mechanism will certainly be a lot messier, involving enzyme-substrate intermediates):
CO2 + H20 <==> H2CO3 (occurs without catalysis, but can be sped up by carbonic anhydrase) H2CO3 + NADH + H+ <==> HCOOH + NAD+ + H2O (catalyzed by formate dehydrogenase) HCOOH + NADH + H+ <==> HCHO + NAD+ + H2O (catalyzed by formaldehyde dehydrogenase) HCHO + NADH + H+ <==> CH3OH + NAD+ (catalyzed by alcohol dehydrogenase)
Net reaction: CO2 + 3NADH + 3H+ <==> CH3OH + 3NAD+ + H2O
I think that's balanced. Biochemists are often lax about mentioning hydrogen ions and water molecules in a reaction because it's generally assumed that they're present in abundance in biological conditions.
What a coincidence. I just went to a lecture today about the determination of the proximal-distal axis and the anterior-posterior axis of limbs in vertebrates. The prime candidate for the determining factor for the anterior-posterior axis (i.e.,from thumb to pinky) is Sonic hedgehog. Unfortunately, you can't do a knockout experiment because without Sonic hedgehog you won't get proximal-distal development (from shoulder to hand.) I wonder if they're using this technique to figure it out?
The theory is pretty old. Some of it was fleshed out as early as the '30s and '40s. These genetic switches are how genes are commonly regulated in biological systems. A textbook example of this is the lambda phage, a virus that infects bacteria, where the cI and the cro gene products act antagonistically, and an external stimulus determines which one wins out, and whether the virus stays in the bacterial chromosome, or whether it decides to leave (killing the bacterium in the process) A lot of the development of vertebrates is regulated in a similar (though at times more complicated) fashion.
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.
"Usually the major problem with antiviral drugs is safety," [Dr. Catherine Laughlin] says. "It's hard to find something that kills the virus and doesn't kill the cell.... There are no similar cellular processes in the body. But you never know."
Once we have the entire sequence, we WILL know (well, realistically speaking, probably not until we figure out how to predict protein folding, too, but it's a big step to getting there), and it'll make designing drugs like this even easier. Add in the technique of DNA shuffling (sexual PCR), and we might actually have a chance at keeping pace with evolution.
This is how protease inhibitors were developed. The time lag in anti-HIV drug development is more due to difficulties with drug delivery systems than with designing the active molecule itself.
While HIV and the rhino virus aren't particularly homologous, I would imagine the principles would be the same. As soon as we started using protease inhibitors against HIV, multiple resistant strains quickly developed. And these drugs were designed in a similar fashion as Pleconaril, through molecular modeling of binding sites. This same type of rapid evolution is what is foiling drugs that are trying to block HIV's entry, which were also developed through molecular modeling. And this rapid evolution occurs even though HIV has a very limited genome, such that genes even overlap each other. You would think that minor mistakes in copying the genome would inactivate the virus, but it doesn't.
The rhino virus also exhibits rapid genetic change. This is the main reason why we never develop immunity to them. We never get hit by the same one twice. I don't even want to imagine how much Pleconaril will accelerate their evolution.
You probably wouldn't be able to get infinite progeny from a single zygote, because you'd eventually run out of cytoplasm. In the early stages of development of most animals, cells divide rapidly but don't grow, so that each time you split the embryo, you'd get half the amount of cytoplasm you started with.
Well, implantation of in-vitro fertilized embryos is hard anyway. This is the same strategy employed at fertility clinics. And even the survival of a naturally conceived embryo isn't guaranteed. It's estimated that 15%-20% of all human conceptions end in spontaneous abortion or stillbirth. Maybe part of it is because of maternal immune response, but most of the time we have no idea why it happens, though we suspect genetic malformations.
As long as the hormone concentrations in the mother are right, so that its body thinks it's pregnant, it will send the appropriate factors to the uterus, regardless of whether or not the embryo is of the correct species, or even if there isn't an embryo there. (Immunologists sometimes work with so called pseudo-pregnant mice.) It's mostly the immune response that would've been the problem, but there is always an immune response, even in naturally conceived embryos. A number of procedures could have been performed in order to control the immune response, such as plasmaphoresis of the mother or fetal blood transfusion, things which might also be done in the case of an Rh- mother carrying an Rh+ baby.
Galileo in fact thought that his discoveries glorified God, and was a devout Christian to the end of his days. The story of Galileo isn't really about religion versus science at all, but about the Establishment versus Free-Thinking. The Church, which was at the time a powerful secular agency, on par with monarchies and empires, thought he was a threat to their power, and so had to silence him. The Church officials cared little for the truth; they were more interested in sustaining their cushy lifestyles.
Science and Religion are not inherently at odds with one another. If practiced properly, they will both lead to different, only slightly overlapping parts of the truth. If anything, Science has the more limited scope of the two. It doesn't have grand ambitions of discovering the Meaning of Life. All science wants to know is how things work. It can't tell us anything about what we can't observe--that is its inherent limitation, and it's what makes it such a powerful method that is accessible to everyone. Discerning the meaning of it all, and figuring out humanity's place in the universe, is left to the philosophers and the theologians.
Fact is, we have no idea what happened before the Big Bang. Was the Big Bang the act of a god? Was it some super-entity sneezing? Did another universe exist before then, that had gotten all squished in the Big Crunch, only to evolve into our own universe? Science will never know, because we will never be able to observe what happened before the Big Bang. If you can't observe it, you can't prove it, and therefore science doesn't have anything to do with it. The Big Bang cannot prove or disprove the existence of God if you are being scientifically rigorous.
It still is science fiction
on
Planet Gattaca
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At least the idea of "creating" life is. Despite the claims, what is possible now is not a significant innovation. It is only a twist on existing genetic experiments. We've been knocking out genes from all types of organisms for years, from bacteria to mice. This is precisely what molecular genetic researchers do. We've also been "creating" new species for much longer than that, through domestication of animals, and more recently, through our uncontrolled use of antibiotics, resulting in microorganisms that never existed before. I don't particularly see what is so profound about knocking out genes from a particular bacterium. While we may have indeed come up with the minimum nucleic acid requirements for life, this does nothing to address the protein, lipid, mineral, and ionic salt requirements. Genes are still just a small part of creating life. As long as we are utilizing pre-existing living materials, how can we possibly claim to be creating anything? This is no more profound than the ability to create life by having sex.
What would be quite impressive would be abiogenesis. But right now we don't even have the technology to chemically synthesize an entire gene, much less an entire genome, even of the simplest organism. So far, we haven't figured out how keep the base pairs from breaking apart in chemically synthesized, long DNA chains. We'd also have to figure out how to chemically synthesize proteins and long polypeptide chains, in order to generate the required replication, transcription, and translation machinery. Right now, we can't do much better than oligopeptides, and even if we could, things don't always fold properly in vitro. Finally, we'd have to figure out how to chemically synthesize a proper phospholipid bilayer, which is probably the most difficult technical challenge of them all. I'm not saying abiogenesis is impossible (it had to have happened at least once, right?), but we are nowhere near that, and until we are, how can we say we are creating life de novo?
As to the topic of DNA sequencing, perhaps this is probably closer to the idea of Gattaca imitating reality. Health insurance companies do already use data about pre-existing conditions to screen applicants. But I'm sure this has been going on since before we had access to sequence data. I don't particularly see what will change. The completion of the Human Genome Project will not be this magical key that will suddenly allow us to manipulate life at our whim. Aside from the arduous technical difficulties of genetic engineering, just because we have sequence info doesn't mean we understand what's going on. What will be more profound than the Project itself will be the research it will spawn. It will surely take much longer to understand the genome than it will take to just sequence it. The Project will mean nothing if this subsequent research doesn't happen.
As to the idea of mapping genes of populations, this is also nothing new. Mapping does not necessarily mean sequencing. (Considering how long the Human Genome Project is taking, it would take over a million years to sequence every human inhabitant of Iceland) We've been mapping genes even before we knew exactly what genes were, even before we knew how to sequence. This is basically what Mendel did, and is what Morgan is known for. This is what doctors do when they are screening for hereditary diseases--they try to construct pedigrees, and all the information in a pedigree is enough to make a rough genetic map. Indeed this is probably another thing that will be more profound than the Human Genome Project itself: merging our rough genetic maps with the sequence data, which will also take a considerably long time. And I can't see what is particularly nefarious about this. Iceland isn't run by a dictatorship, right? As long as that's the case, individuals would have to give their consent in order to be mapped. While there are ethical concerns with genetic mapping, such as revealing true parentage, or high probability of a fatal disease, I can't see how it will degenerate into a Gattaca-style world. It is quite obvious that we are more than our genotypes. For one thing, the things we die from have very strong environmental components. In industrialized countries, not counting auto-accidents, people tend to die from heart disease and cancer. While they do have genetic components, it is not a 100% guarantee. You can protect yourself by eating right and not staying out in the sun, for example. In developing countries, people mostly die from infection and starvation, also environmentally controlled. For another thing, we haven't even roughly mapped things like intelligence to the genome. And in any case, the environmental component of that is very sizeable. Important neural development such as myelination and activity dependent synapse elimination occur mostly after birth, in response to environmental stimuli. Genes undoubtedly set the stage, but they aren't responsible for the performance itself.
I think it makes a big difference that these things are issues of the distant future, meaning that we are still at least one paradigm shift away from having to consider these things. While I'm not saying it's useless to consider these things now, it doesn't have the urgency that things like gene patents or terminator genes do. For all we know, everything we are talking about now might be completely untrue. We might be like people in ancient days arguing over whether there was an abyss or a wall at the edge of the world. It probably was important, in terms of philosophy, but until they actually tried to find the edge of the world, it didn't really have much of bearing on reality, which turned out to be quite different. In the same way, these debates may be over something that isn't real at all, or we may end up overlooking some fact that will become painfully obvious. The point is, we aren't there yet, and until we do get there, everything we say now is completely up in the air and possibly quite useless in terms of defining public policy and ethical concerns.
But I think Katz is on the right track by mentioning literature, specifically science-fiction. This is precisely where this debate should be right now. This genre has traditionally been the forum for arguing highly speculative issues. Asimov long ago explored issues of robotics and AI, even though we haven't even gotten there yet. Clarke has perhaps been a strong inspiration for many of our missions to space, generating ideas we are still nowhere near attaining. Cyberpunk has perhaps anticipated many issues regarding our Net-connected world. Right now, these issues about genetic engineering are rife for creative exploration, and indeed there are many science-fiction stories written in this vein. But I think technology needs to progress a little further before we can realistically start debating actual policies and laws, and whether this is a good thing or a bad thing. How can we hope to correctly anticipate making a decision when we don't have the capability to make that decision yet?
Isn't life low in entropy, since an organism is much more highly ordered than, say, rocks or ice? (Although I realize that the net result of metabolism is still an increase of entropy, because waste products tend to be highly disordered.) And wouldn't planetary atmospheres on a barren world be high in entropy, because they are the result of chemical equilibration (delta G = 0)? (This would be in contrast to atmospheres of life bearing planets which would be at a steady state)
With this in mind, could these be ways to detect life? Either to look for pockets of matter that are highly ordered amidst pockets of matter that have high disorder, or to look for phenomena that are at steady state, not at equilibrium?
It seems we are again halfway closer to the goal of figuring out the origin of life. But maybe it really is a case of Zeno's paradox. We thought we figured it out when we synthesized amino acids and nucleic acids in vitro, but there always seems to be that little bit that we don't understand.
From reading biology-related stories on Slashdot and their attedant comments, I feel that there is this notion that all we need is the genetic information, and the rest will follow. But I think that the nature of life does not rest in nucleic acids, but in the unique self-assembling properties of certain organic compounds, much of which we know little about.
While I'm not saying that what these scientists propose to do is impossible, I really think that it is in the league of trying to figure out faster-than-light starflight. At least, if they are really intending to create life de novo, from a naked, chemically synthesized chromosome. For one thing, they will need to figure out a way to make incredibly long strands of DNA. Even if every single one of these critical genes were only 500bp long, this minimal genome would still require 150kbp, magnitudes of order longer than our current techniques can manage. But that would be the least of the difficulties. So far, we haven't gotten DNA to replicate itself without proteins. And, at least in existing organisms, you can't generate proteins without having pre-existing proteins. A classic chicken-and-egg problem. Add to this the fact that you can't have any metabolism anyway if you don't have a proper phospholipid bilayer, which also requires the presence of proteins to maintain the required internal environment, and it turns out to be quite a formidable task.
But if all these scientists are going to do is take these minimal genes out and resplice them into an optimized chromosome, suck out the DNA of an existing bacterium and plug-in their custom module, utilizing the existing replication, transcription, and translation machinery, can we really say this is creating life? Then this becomes no different from in-vitro fertilization and only a little more difficult than simply having sex.
Jon Katz's article seems to belie a misunderstanding of the Human Genome Project and of genetics in general, and it doesn't do much to address issue relevant to today. While undeniably, knowing the entire human genome can eventually lead to trying to make changes in it, Katz makes it sound as if the Project itself is an attempt at eugenics. All we will have in three years or less is an incredibly long string made up of four letters. In of itself, it will not tell us anything that we don't already know or at least have an idea of. There will be no magical messages, no sudden insights afforded by this knowledge. The things that will benefit from sequence info are things we are already studying, and while it will be useful, it will certainly not be the end-all-be-all. For example, the gene that most biologists think (not all agree!) causes cystic fibrosis was discovered before the Project even started, and we even had an idea as to what it did before we got any sequence info. Not to say that sequence info isn't helpful--it helped narrow down what the most common mutation was--but it requires a lot more than sequence info to understand what these things do and how to control them. Even with the sequence info, we don't have a conclusive understanding of why a mutation in CFTR causes the symptoms that it does. Same thing with Huntington's Disease. Sure, we've found the mutation, but we have no idea what the gene does. We just gave the gene product the name huntingtinin because its function is unknown, even though we have the sequence
And these are single-gene diseases, things that have very clear-cut phenotypes, things that we knew about long before the Project even started. Indeed, some of these things had already been sequenced. But how much more daunting would it be to try to come up with a genetic basis for things that we don't even have strict (or even vague, for that matter) biological/physical definitions for, like intelligence? I'm not saying it won't happen, but I think we'll have decades, if not centuries, to worry about it.
While cosmetic uses (as opposed to medical uses) for gene engineering will probably happen, it won't be the thrust of the technology, anymore than it is with surgery today. I'm pretty sure most scientists will be engrossed with solving existing problems before mucking around trying to create the "perfect baby." After all, if you had the money to fund a project, would you give money to something that would help your children but not yourself, or would you give money to something that would help you as well? And I really think it would be a one or the other situation, at least for now. Doing genetic engineering in somatic cells would be a lot different from doing it in germ cells.
Add to this the complication that the most pressing disorders are not of pure genetic origin, such as heart disease and cancer, and the idea of perfecting the human race simply through genetics becomes absurd. Heart disease has obvious environmental factors, and if you don't correct those, no amount of genetic engineering will save you. In fact, people without predispositions for heart disease can screw themselves over eating the wrong foods. And while some types of cancer have obvious hereditary components, all they do is set you up for the fall, like in retinoblastoma, Li Fraumeni's disease, or breast cancer. Environmental factors are the straws that break the camel's back--these are mainly light from the sun and oxygen, things you cannot avoid. Our DNA is being damaged every hour. It's just that most of these damaged cells are meant to die anyway, but sometimes you get unlucky. If you don't die of something else, if we somehow magically cure every other disease on the planet, you will die of cancer. The only way we can solve it is if we find a way to store genetic information in a more robust form than DNA--something science fiction writers like talking about. So while I'm not going to say it's impossible, that's certainly a long way off.
In addition, a lot of less common maladies are de novo mutations. While they can be inherited, a large number of cases just pretty much come out of thin air, from completely normal parents, conditions like neurofibramatosis and Down's Syndrome. In the case of Down's Syndrome, there is very little you can do about it in terms of raw sequence data. Someone will have to figure out why non-disjunction occurs with this chromosome so often--but even that's not that helpful because non-disjunction happens often with every chromosome. It's just that Down's Syndrome is the only one that is compatible with life. Everything else is spontaneously aborted, sometimes even without the mother knowing she was pregnant. So while maybe sequence info can help--we might figure out how certain sequences are important as binding sites in mitosis--sequence info will not be the sole answer. Some creative scientist will have to figure it out.
The idea of eugenics is pretty anathema to the current scientific mindset. Sure, there are some scientists out there who believe in it, but I really think that what we know is against them. As pessimistic as it sounds, I'm pretty sure Nature will figure out some way to kill us even if we somehow eliminated all disorders we know about now. Look at tuberculosis. We thought we had it licked, and now it's coming back. Look at HIV. Everything we throw at it just makes it stronger. Our drugs are in fact making it evolve into something less controllable.
Concern about insurance companies demanding sequence info, and discriminating on the basis of it is perhaps more relevant to current issues. Obviously, this is not going to happen very soon, considering that the human genome project is taking as long as it is. It is very unlikely that everyone will have to wait 10 years to get their sequence done and therefore get approved. But let's say we do figure out a way to do it in a more reasonable time frame. Well, this is nothing new--and I have issues with the existing system. Insurance companies already discriminate according to pre-existing conditions. Got diabetes? Too bad. Got thyroiditis? Oh well. How sequence info will make this better or worse is anybody's guess, but it's not going to turn us overnight into Aldous Huxley's Brave New World. Genetic screening already happens. People choose to abort fetuses that are "defective." Here's a novel case: an achondroplasic couple wanted an achondroplasic child, and wanted to abort it they had a normal child. But karyotypes for Down's are practically routine. I don't see us filing in line for soma just yet. (Or wait. Maybe that's what TV is...) I agree that the Human Genome Project and the ethics of what genetic engineering we are doing now are important topics to think about. But this article does nothing to explore issues regarding these topics that are relevant today. Like how drug companies are patenting genes. Or how some biotech companies are trying to make designer seeds that won't reproduce. Or how insurance companies are already using medical information to discriminate and basically deny treatment, using the rudimentary genetic screening we know now. There are a lot of issues that are much closer than the fear of someone trying to design supermen. I say first things first.
Well, you can still die from a little cut today, even with penicillin, at least in a hospital. Obviously not as easily, but it happens. And this is in an industrialized nation. It probably still is just as bad as it was back then in developing nations. Penicillin is mostly useless now a days anyway.
But I don't think the point is to stop using antibiotics, anymore than we should stop genetic engineering, simply because bad things will happen. The point is that just because we can use them doesn't always mean we should, and that things we think of as A Good Thing aren't always.
at least have an idea of. There will be no magical messages, no sudden insights afforded by this knowledge. The things that will benefit from sequence info are things we are already studying, and while it will be useful, it will certainly not be the end-all-be-all. For example, the gene that most biologists think (not all agree!) causes cystic fibrosis was discovered before the Project even started, and we even had an idea as to what it did before we got any sequence info. Not to say that sequence info isn't helpful--it helped narrow down what the most common mutation was--but it requires a lot more than sequence info to understand what these things do and how to control them. Even with the sequence info, we don't have a conclusive understanding of why a mutation in CFTR causes the symptoms that it does. Same thing with Huntington's Disease. Sure, we've found the mutation, but we have no idea what the gene does. We just gave the gene product the name huntingtinin because its function is unknown, even though we have the sequence
And these are single-gene diseases, things that have very clear-cut phenotypes, things that we knew about long before the Project even started. Indeed, some of these things had already been sequenced. But how much more daunting would it be to try to come up with a genetic basis for things that we don't even have strict (or even vague, for that matter) biological/physical definitions for, like intelligence? I'm not saying it won't happen, but I think we'll have decades, if not centuries, to worry about it.
While cosmetic uses (as opposed to medical uses) for gene engineering will probably happen, it won't be the thrust of the technology, anymore than it is with surgery today. I'm pretty sure most scientists will be engrossed with solving existing problems before mucking around trying to create the "perfect baby." After all, if you had the money to fund a project, would you give money to something that would help your children but not yourself, or would you give money to something that would help you as well? And I really think it would be a one or the other situation, at least for now. Doing genetic engineering in somatic cells would be a lot different from doing it in germ cells.
Add to this the complication that the most pressing disorders are not of pure genetic origin, such as heart disease and cancer, and the idea of perfecting the human race simply through genetics becomes absurd. Heart disease has obvious environmental factors, and if you don't correct those, no amount of genetic engineering will save you. In fact, people without predispositions for heart disease can screw themselves over eating the wrong foods. And while some types of cancer have obvious hereditary components, all they do is set you up for the fall, like in retinoblastoma, Li Fraumeni's disease, or breast cancer. Environmental factors are the straws that break the camel's back--these are mainly light from the sun and oxygen, things you cannot avoid. Our DNA is being damaged every hour. It's just that most of these damaged cells are meant to die anyway, but sometimes you get unlucky. If you don't die of something else, if we somehow magically cure every other disease on the planet, you will die of cancer. The only way we can solve it is if we find a way to store genetic information in a more robust form than DNA--something science fiction writers like talking about. So while I'm not going to say it's impossible, that's certainly a long way off.
In addition, a lot of less common maladies are de novo mutations. While they can be inherited, a large number of cases just pretty much come out of thin air, from completely normal parents, conditions like neurofibramatosis and Down's Syndrome. In the case of Down's Syndrome, there is very little you can do about it in terms of raw sequence data. Someone will have to figure out why non-disjunction occurs with this chromosome so often--but even that's not that helpful because non-disjunction happens often with every chromosome. It's just that Down's Syndrome is the only one that is compatible with life. Everything else is spontaneously aborted, sometimes even without the mother knowing she was pregnant. So while maybe sequence info can help--we might figure out how certain sequences are important as binding sites in mitosis--sequence info will not be the sole answer. Some creative scientist will have to figure it out.
The idea of eugenics is pretty anathema to the current scientific mindset. Sure, there are some scientists out there who believe in it, but I really think that what we know is against them. As pessimistic as it sounds, I'm pretty sure Nature will figure out some way to kill us even if we somehow eliminated all disorders we know about now. Look at tuberculosis. We thought we had it licked, and now it's coming back. Look at HIV. Everything we throw at it just makes it stronger. Our drugs are in fact making it evolve into something less controllable.
Concern about insurance companies demanding sequence info, and discriminating on the basis of it is perhaps more relevant to current issues. Obviously, this is not going to happen very soon, considering that the human genome project is taking as long as it is. It is very unlikely that everyone will have to wait 10 years to get their sequence done and therefore get approved. But let's say we do figure out a way to do it in a more reasonable time frame. Well, this is nothing new--and I have issues with the existing system. Insurance companies already discriminate according to pre-existing conditions. Got diabetes? Too bad. Got thyroiditis? Oh well. How sequence info will make this better or worse is anybody's guess, but it's not going to turn us overnight into Aldous Huxley's Brave New World. Genetic screening already happens. People choose to abort fetuses that are "defective." Here's a novel case: an achondroplasic couple wanted an achondroplasic child, and wanted to abort it they had a normal child. But karyotypes for Down's are practically routine. I don't see us filing in line for soma just yet. (Or wait. Maybe that's what TV is...) I agree that the Human Genome Project and the ethics of what genetic engineering we are doing now are important topics to think about. But this article does nothing to explore issues regarding these topics that are relevant today. Like how drug companies are patenting genes. Or how some biotech companies are trying to make designer seeds that won't reproduce. Or how insurance companies are already using medical information to discriminate and basically deny treatment, using the rudimentary genetic screening we know now. There are a lot of issues that are much closer than the fear of someone trying to design supermen. I say first things first.
This is untrue. Organisms have an entire system of genetically programmed cell death, called "apoptosis."
True. But apoptosis is basically a mechanism for cellular euthanasia, enacted in cells that would die anyway, or cause death in the whole organism if left unchecked. Failure of apoptosis can lead to such things like cancer, immune disease, and a host of other disorders. While cancer is cellular immortality, the whole organism will surely die.
Aging is a consequence of being in an oxidizing environment and being constantly bombarded by radiation, among other things. These things damage DNA, and the only reason we don't suffer more from it is exactly because of apoptosis.
Removing the program for apoptosis will probably do nothing to lengthen our lifespans. Neither will adding telomerase. Even organisms that don't have these things, like bacteria, succumb to entropy. It's simply statistically impossible to go on replicating DNA faithfully forever and expect to remain functional. Even with the multifarious repair mechanisms evolution has come up with, there is DNA damage. That's why evolution developed multiple, redundant chromosomes, sex, and apoptosis. Death is not a genetic constraint. It's simply physical.
Just from a purely economic standpoint, does it really make sense to engineer perfect babies? Sure, you'll make a ton of cash for one generation, when all the rich people have theirs done, but after that, you've essentially obsoleted yourself. Wouldn't you make a lot more money by doing somatic genetic engineering instead of altering the germ line? You'd be able to treat everyone who is alive today, AND you'd have to treat their children too, and their children's children, etc. And since altering somatic cells would probably be a lot cheaper than creating a perfect child de novo, you'd probably be able to offer your services to a much larger market. Not only the ultra-rich would be able to afford it. And no one can blame you for destroying the human genome (which is a pretty good possibility if you start mucking around with the germ-line).
Seriously, if you were a rich guy with a predisposition for cancer, would you fork over a ton of cash just so your kid wouldn't have cancer? Or would you rather fork over that ton of cash so that YOU wouldn't have cancer? I think that once the genome is complete, we'll probably spend more time treating existing conditions than doing cosmetic genetic engineering and designing the "perfect" human, because that's where the funding is going to be.
Someday, we may even greatly slow down the aging process, by identifying which genes are responsible for certain types of bodily decay.
There are no genes that encode for aging or death. It is just a natural consequence of thermodynamics. Medical intervention will probably be more important than genetic intervention in determining our lifespans.
The funny thing is, this isn't a dead issue today. There IS a dilemma regarding the dispensation of antibiotics and antiseptics. They aren't unilaterally good. The overuse of antibiotics has generated drug resistant microorganisms that would never have existed otherwise.
Is there a link to the actual article? Most of my questions will probably be answered by it, but I'll ask them anyway...
I don't know too much about the brain, but it strikes me that the conclusion of the study doesn't really say anything about intelligence, or even anything about the correlation between profession and number of synapses, given how they measured the synapses. If they took brain tissue from an important part of the subjects' brain, wouldn't it affect the subjects drastically? If it isn't from an important part of the brain, then how can we be sure the finding has any meaning? Just because a certain neuron is being synapsed by a thousand axons doesn't mean that neuron is even being used. The fact that there are a lot of synapses might even demonstrate that that particular circuit isn't being used. We start out with more synapses prenatally then when we're adults. Then our connections are refined, so that a large number of these synapses are removed. This weeding out process is determined by the amount of electrical activity passing through a neuron. The multiplicity of synapses is part of the reason why we can't walk (or do much of anything) when we're born (that, and not having finished myelination.) Paring them down is what allows us to control our musculature. I realize brain synapses are drastically different from neuromuscular junctions, but I think the principle is the same. It's not the quantity, it's how they're connected that makes a big difference, not to mention the type of synapse they are.
I don't know the exact etymology of the term "junk DNA," but it probably stems from a protein-centric view of molecular biology, which was the standard among biologists until Watson and Crick did their thing, and it has taken quite a while for biology to rid itself of this bias. In this viewpoint, any nucleic acid that doesn't get translated is "junk." We know a lot more than when the term was coined, and although the term still remains, it's no longer a useful one. We do know that a lot of DNA that doesn't get translated or even transcribed do in fact have distinct structural functions, like centromeres and telomeres. We know other parts are involved in the regulation of gene expression. Sequences that flank ORFs either bind proteins that are transcription factors, or themselves form secondary structure. And while the presence of introns is still mostly mysterious, we do know that for some reason in some cases in-vitro, they can enhance the uptake and expression of foreign DNA in cells.
Still, there are sequences that really do seem completely useless and can even have deleterious effects, like the Alu and L1 families of pseudogenes, which can replicate themselves autonomously, and randomly insert copies of themselves into the genome, on rare occasions breaking genes. There are around 500,000 copies of Alu in the genome, and about 10,000 copies of L1, for a total of 210 Mbp out of 3Gbp of total DNA. This dwarfs the estimated 120 Mbp of DNA that encodes proteins. And besides Alu and L1, there are tons of other pseudogenes scattered along the gene, essentially the cruft of evolution.
Thus, the junk is not necessarily useless, but neither is all the DNA necessarily useful. And of course it depends by what you mean as useful.
Slashdot Mirror
I suppose this is for all those people who are leery of using replication-incompetent retroviruses, which right now are much better at sending their payload to specific tissues in-vivo, but it's not entirely certain that they can't mutate and regain their replicative abilities.
Mutations are simply the result of alterations to DNA. DNA, like all molecules, rapidly interconverts between several energetically equivalent conformations. Specifically, the bases that comprise DNA can interconvert between imidine forms and amino forms. (And the base pairing rules change depending on which form the base adopts.) As long as nothing interacts with the base, it exists, in a sense, in an indeterminate state (This might serve as the mechanism for "sampling" mutations.) Only when the base interacts with another molecule, such as its base pair, does the base "crash out" of the "quantum foam" into one of those conformations. Whatever it is interacting with, whether a mutagen, an enzyme, or its base pair, actually forces it to adopt a conformation. (And vice-versa. Although in reality, I imagine that it still isn't really locked into one conformation, it's just that the probability of it existing in that conformation has increased, while the probability of it existing in the other conformations has decreased.)
It is because of base-pairing that mutations don't happen more often, but when DNA is replicating, or being transcribed, the bases can often be in an unpaired (and therefore indeterminate) state. When the base is again paired, it might have adopted the "mutated" conformation instead of the (normal) "wild-type" conformation. But even then, most mutations are still reversible because of the energy available in the system (manifested through repair enzymes and the concomitant hydrolysis of ATP)
So in a sense, every single base in every single cell in your body is rapidly fluctuating between a "wild-type" state and a "mutated" state. So every single moment, a sort of natural selection occurs in that the combinations of conformations that favor survival is selected for. But here is where "quantum evolution" might be flawed, if what the article seems to implying is true. The article seems to say that there is some novel principle that provides this selective pressure--some force that favors life. But I think the nature of this selective pressure is a lot simpler. I think it's just thermodynamics.
Whether or not a mutation persists depends on whether it is energetically favorable or not. Normally, the wild-type, particularly when it is interacting with its base pair, is energetically favored, but put in energy, like in the form of a gamma ray, and the mutant conformation can be favored. Of course, the mutation can always be repaired, but this too depends on the energy available in the cell. If the cell doesn't have a lot of ATP to spare, and the mutation doesn't kill it right then and there, it is likely that the mutation will persist.
This process is pretty much what directs evolution in single-celled organisms (which pretty much make up the majority of all life forms and whose history pretty much dominates all of evolution), and it works pretty much the same in multicellular organisms, except that only a small fraction of cells actually get to propagate mutations, and a lot of it gets covered up by sex anyways. Mutation isn't really an all-or-nothing event, but more a summation of probabilities, which don't actually get locked in until it's time for the mutation to be propagated. And all this applies to acellular DNA, too. Since we know that DNA can be synthesized abiotically from simple gases and lightning, and that the ability to replicate is a direct consequence of the structure of DNA, it isn't really that much of a leap to imagine the evolution of a nucleic acid into a single celled organism. It's really all just thermodynamics.
One might argue that thermodynamics actually favors the destruction of life (i.e., since disorder ever increases), and in a sense it's true since we all die, but luckily thermodynamics doesn't say anything about how fast something happens. Using the hydrolysis of proteins as an example: protein + H2O --> amino acids, which is exergonic, may seem to prove this even further, but this forgets to include the fact that in protein synthesis, ATP is hydrolyzed too, and this actually makes it thermodynamically favorable to make proteins. The reason life occurs is because thermodynamics says it can, and given enough time (namely, billions of years), anything that thermodynamics says can happen will, no matter how improbable you think it is. So evolution isn't really random at all, and you don't need to look farther than college chemistry to see why.
Why don't they just couple this with, say, glycolysis or the electron transport chain so they can regenerate NADH as much as they want? Couple these to photosynthesis, and you could cut CO2 emissions even further. Use the enzymes out of some archaebacteria, and you could filter out nitrogen or sulfur byproducts as well.
CO2 + H20 <==> H2CO3
(occurs without catalysis, but can be sped up by carbonic anhydrase)
H2CO3 + NADH + H+ <==> HCOOH + NAD+ + H2O
(catalyzed by formate dehydrogenase)
HCOOH + NADH + H+ <==> HCHO + NAD+ + H2O
(catalyzed by formaldehyde dehydrogenase)
HCHO + NADH + H+ <==> CH3OH + NAD+
(catalyzed by alcohol dehydrogenase)
Net reaction: CO2 + 3NADH + 3H+ <==> CH3OH + 3NAD+ + H2O
I think that's balanced. Biochemists are often lax about mentioning hydrogen ions and water molecules in a reaction because it's generally assumed that they're present in abundance in biological conditions.
What a coincidence. I just went to a lecture today about the determination of the proximal-distal axis and the anterior-posterior axis of limbs in vertebrates. The prime candidate for the determining factor for the anterior-posterior axis (i.e.,from thumb to pinky) is Sonic hedgehog. Unfortunately, you can't do a knockout experiment because without Sonic hedgehog you won't get proximal-distal development (from shoulder to hand.) I wonder if they're using this technique to figure it out?
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.
"Usually the major problem with antiviral drugs is safety," [Dr. Catherine Laughlin] says. "It's hard to find something that kills the virus and doesn't kill the cell.... There are no similar cellular processes in the body. But you never know."
Once we have the entire sequence, we WILL know (well, realistically speaking, probably not until we figure out how to predict protein folding, too, but it's a big step to getting there), and it'll make designing drugs like this even easier. Add in the technique of DNA shuffling (sexual PCR), and we might actually have a chance at keeping pace with evolution.
This is how protease inhibitors were developed. The time lag in anti-HIV drug development is more due to difficulties with drug delivery systems than with designing the active molecule itself.
The rhino virus also exhibits rapid genetic change. This is the main reason why we never develop immunity to them. We never get hit by the same one twice. I don't even want to imagine how much Pleconaril will accelerate their evolution.
You probably wouldn't be able to get infinite progeny from a single zygote, because you'd eventually run out of cytoplasm. In the early stages of development of most animals, cells divide rapidly but don't grow, so that each time you split the embryo, you'd get half the amount of cytoplasm you started with.
As long as the hormone concentrations in the mother are right, so that its body thinks it's pregnant, it will send the appropriate factors to the uterus, regardless of whether or not the embryo is of the correct species, or even if there isn't an embryo there. (Immunologists sometimes work with so called pseudo-pregnant mice.) It's mostly the immune response that would've been the problem, but there is always an immune response, even in naturally conceived embryos. A number of procedures could have been performed in order to control the immune response, such as plasmaphoresis of the mother or fetal blood transfusion, things which might also be done in the case of an Rh- mother carrying an Rh+ baby.
Science and Religion are not inherently at odds with one another. If practiced properly, they will both lead to different, only slightly overlapping parts of the truth. If anything, Science has the more limited scope of the two. It doesn't have grand ambitions of discovering the Meaning of Life. All science wants to know is how things work. It can't tell us anything about what we can't observe--that is its inherent limitation, and it's what makes it such a powerful method that is accessible to everyone. Discerning the meaning of it all, and figuring out humanity's place in the universe, is left to the philosophers and the theologians.
Fact is, we have no idea what happened before the Big Bang. Was the Big Bang the act of a god? Was it some super-entity sneezing? Did another universe exist before then, that had gotten all squished in the Big Crunch, only to evolve into our own universe? Science will never know, because we will never be able to observe what happened before the Big Bang. If you can't observe it, you can't prove it, and therefore science doesn't have anything to do with it. The Big Bang cannot prove or disprove the existence of God if you are being scientifically rigorous.
What would be quite impressive would be abiogenesis. But right now we don't even have the technology to chemically synthesize an entire gene, much less an entire genome, even of the simplest organism. So far, we haven't figured out how keep the base pairs from breaking apart in chemically synthesized, long DNA chains. We'd also have to figure out how to chemically synthesize proteins and long polypeptide chains, in order to generate the required replication, transcription, and translation machinery. Right now, we can't do much better than oligopeptides, and even if we could, things don't always fold properly in vitro. Finally, we'd have to figure out how to chemically synthesize a proper phospholipid bilayer, which is probably the most difficult technical challenge of them all. I'm not saying abiogenesis is impossible (it had to have happened at least once, right?), but we are nowhere near that, and until we are, how can we say we are creating life de novo?
As to the topic of DNA sequencing, perhaps this is probably closer to the idea of Gattaca imitating reality. Health insurance companies do already use data about pre-existing conditions to screen applicants. But I'm sure this has been going on since before we had access to sequence data. I don't particularly see what will change. The completion of the Human Genome Project will not be this magical key that will suddenly allow us to manipulate life at our whim. Aside from the arduous technical difficulties of genetic engineering, just because we have sequence info doesn't mean we understand what's going on. What will be more profound than the Project itself will be the research it will spawn. It will surely take much longer to understand the genome than it will take to just sequence it. The Project will mean nothing if this subsequent research doesn't happen.
As to the idea of mapping genes of populations, this is also nothing new. Mapping does not necessarily mean sequencing. (Considering how long the Human Genome Project is taking, it would take over a million years to sequence every human inhabitant of Iceland) We've been mapping genes even before we knew exactly what genes were, even before we knew how to sequence. This is basically what Mendel did, and is what Morgan is known for. This is what doctors do when they are screening for hereditary diseases--they try to construct pedigrees, and all the information in a pedigree is enough to make a rough genetic map. Indeed this is probably another thing that will be more profound than the Human Genome Project itself: merging our rough genetic maps with the sequence data, which will also take a considerably long time. And I can't see what is particularly nefarious about this. Iceland isn't run by a dictatorship, right? As long as that's the case, individuals would have to give their consent in order to be mapped. While there are ethical concerns with genetic mapping, such as revealing true parentage, or high probability of a fatal disease, I can't see how it will degenerate into a Gattaca-style world. It is quite obvious that we are more than our genotypes. For one thing, the things we die from have very strong environmental components. In industrialized countries, not counting auto-accidents, people tend to die from heart disease and cancer. While they do have genetic components, it is not a 100% guarantee. You can protect yourself by eating right and not staying out in the sun, for example. In developing countries, people mostly die from infection and starvation, also environmentally controlled. For another thing, we haven't even roughly mapped things like intelligence to the genome. And in any case, the environmental component of that is very sizeable. Important neural development such as myelination and activity dependent synapse elimination occur mostly after birth, in response to environmental stimuli. Genes undoubtedly set the stage, but they aren't responsible for the performance itself.
I think it makes a big difference that these things are issues of the distant future, meaning that we are still at least one paradigm shift away from having to consider these things. While I'm not saying it's useless to consider these things now, it doesn't have the urgency that things like gene patents or terminator genes do. For all we know, everything we are talking about now might be completely untrue. We might be like people in ancient days arguing over whether there was an abyss or a wall at the edge of the world. It probably was important, in terms of philosophy, but until they actually tried to find the edge of the world, it didn't really have much of bearing on reality, which turned out to be quite different. In the same way, these debates may be over something that isn't real at all, or we may end up overlooking some fact that will become painfully obvious. The point is, we aren't there yet, and until we do get there, everything we say now is completely up in the air and possibly quite useless in terms of defining public policy and ethical concerns.
But I think Katz is on the right track by mentioning literature, specifically science-fiction. This is precisely where this debate should be right now. This genre has traditionally been the forum for arguing highly speculative issues. Asimov long ago explored issues of robotics and AI, even though we haven't even gotten there yet. Clarke has perhaps been a strong inspiration for many of our missions to space, generating ideas we are still nowhere near attaining. Cyberpunk has perhaps anticipated many issues regarding our Net-connected world. Right now, these issues about genetic engineering are rife for creative exploration, and indeed there are many science-fiction stories written in this vein. But I think technology needs to progress a little further before we can realistically start debating actual policies and laws, and whether this is a good thing or a bad thing. How can we hope to correctly anticipate making a decision when we don't have the capability to make that decision yet?
With this in mind, could these be ways to detect life? Either to look for pockets of matter that are highly ordered amidst pockets of matter that have high disorder, or to look for phenomena that are at steady state, not at equilibrium?
From reading biology-related stories on Slashdot and their attedant comments, I feel that there is this notion that all we need is the genetic information, and the rest will follow. But I think that the nature of life does not rest in nucleic acids, but in the unique self-assembling properties of certain organic compounds, much of which we know little about.
While I'm not saying that what these scientists propose to do is impossible, I really think that it is in the league of trying to figure out faster-than-light starflight. At least, if they are really intending to create life de novo, from a naked, chemically synthesized chromosome. For one thing, they will need to figure out a way to make incredibly long strands of DNA. Even if every single one of these critical genes were only 500bp long, this minimal genome would still require 150kbp, magnitudes of order longer than our current techniques can manage. But that would be the least of the difficulties. So far, we haven't gotten DNA to replicate itself without proteins. And, at least in existing organisms, you can't generate proteins without having pre-existing proteins. A classic chicken-and-egg problem. Add to this the fact that you can't have any metabolism anyway if you don't have a proper phospholipid bilayer, which also requires the presence of proteins to maintain the required internal environment, and it turns out to be quite a formidable task.
But if all these scientists are going to do is take these minimal genes out and resplice them into an optimized chromosome, suck out the DNA of an existing bacterium and plug-in their custom module, utilizing the existing replication, transcription, and translation machinery, can we really say this is creating life? Then this becomes no different from in-vitro fertilization and only a little more difficult than simply having sex.
Jon Katz's article seems to belie a misunderstanding of the Human Genome Project and of genetics in general, and it doesn't do much to address issue relevant to today. While undeniably, knowing the entire human genome can eventually lead to trying to make changes in it, Katz makes it sound as if the Project itself is an attempt at eugenics. All we will have in three years or less is an incredibly long string made up of four letters. In of itself, it will not tell us anything that we don't already know or at least have an idea of. There will be no magical messages, no sudden insights afforded by this knowledge. The things that will benefit from sequence info are things we are already studying, and while it will be useful, it will certainly not be the end-all-be-all. For example, the gene that most biologists think (not all agree!) causes cystic fibrosis was discovered before the Project even started, and we even had an idea as to what it did before we got any sequence info. Not to say that sequence info isn't helpful--it helped narrow down what the most common mutation was--but it requires a lot more than sequence info to understand what these things do and how to control them. Even with the sequence info, we don't have a conclusive understanding of why a mutation in CFTR causes the symptoms that it does. Same thing with Huntington's Disease. Sure, we've found the mutation, but we have no idea what the gene does. We just gave the gene product the name huntingtinin because its function is unknown, even though we have the sequence
And these are single-gene diseases, things that have very clear-cut phenotypes, things that we knew about long before the Project even started. Indeed, some of these things had already been sequenced. But how much more daunting would it be to try to come up with a genetic basis for things that we don't even have strict (or even vague, for that matter) biological/physical definitions for, like intelligence? I'm not saying it won't happen, but I think we'll have decades, if not centuries, to worry about it.
While cosmetic uses (as opposed to medical uses) for gene engineering will probably happen, it won't be the thrust of the technology, anymore than it is with surgery today. I'm pretty sure most scientists will be engrossed with solving existing problems before mucking around trying to create the "perfect baby." After all, if you had the money to fund a project, would you give money to something that would help your children but not yourself, or would you give money to something that would help you as well? And I really think it would be a one or the other situation, at least for now. Doing genetic engineering in somatic cells would be a lot different from doing it in germ cells.
Add to this the complication that the most pressing disorders are not of pure genetic origin, such as heart disease and cancer, and the idea of perfecting the human race simply through genetics becomes absurd. Heart disease has obvious environmental factors, and if you don't correct those, no amount of genetic engineering will save you. In fact, people without predispositions for heart disease can screw themselves over eating the wrong foods. And while some types of cancer have obvious hereditary components, all they do is set you up for the fall, like in retinoblastoma, Li Fraumeni's disease, or breast cancer. Environmental factors are the straws that break the camel's back--these are mainly light from the sun and oxygen, things you cannot avoid. Our DNA is being damaged every hour. It's just that most of these damaged cells are meant to die anyway, but sometimes you get unlucky. If you don't die of something else, if we somehow magically cure every other disease on the planet, you will die of cancer. The only way we can solve it is if we find a way to store genetic information in a more robust form than DNA--something science fiction writers like talking about. So while I'm not going to say it's impossible, that's certainly a long way off.
In addition, a lot of less common maladies are de novo mutations. While they can be inherited, a large number of cases just pretty much come out of thin air, from completely normal parents, conditions like neurofibramatosis and Down's Syndrome. In the case of Down's Syndrome, there is very little you can do about it in terms of raw sequence data. Someone will have to figure out why non-disjunction occurs with this chromosome so often--but even that's not that helpful because non-disjunction happens often with every chromosome. It's just that Down's Syndrome is the only one that is compatible with life. Everything else is spontaneously aborted, sometimes even without the mother knowing she was pregnant. So while maybe sequence info can help--we might figure out how certain sequences are important as binding sites in mitosis--sequence info will not be the sole answer. Some creative scientist will have to figure it out.
The idea of eugenics is pretty anathema to the current scientific mindset. Sure, there are some scientists out there who believe in it, but I really think that what we know is against them. As pessimistic as it sounds, I'm pretty sure Nature will figure out some way to kill us even if we somehow eliminated all disorders we know about now. Look at tuberculosis. We thought we had it licked, and now it's coming back. Look at HIV. Everything we throw at it just makes it stronger. Our drugs are in fact making it evolve into something less controllable.
Concern about insurance companies demanding sequence info, and discriminating on the basis of it is perhaps more relevant to current issues. Obviously, this is not going to happen very soon, considering that the human genome project is taking as long as it is. It is very unlikely that everyone will have to wait 10 years to get their sequence done and therefore get approved. But let's say we do figure out a way to do it in a more reasonable time frame. Well, this is nothing new--and I have issues with the existing system. Insurance companies already discriminate according to pre-existing conditions. Got diabetes? Too bad. Got thyroiditis? Oh well. How sequence info will make this better or worse is anybody's guess, but it's not going to turn us overnight into Aldous Huxley's Brave New World. Genetic screening already happens. People choose to abort fetuses that are "defective." Here's a novel case: an achondroplasic couple wanted an achondroplasic child, and wanted to abort it they had a normal child. But karyotypes for Down's are practically routine. I don't see us filing in line for soma just yet. (Or wait. Maybe that's what TV is...) I agree that the Human Genome Project and the ethics of what genetic engineering we are doing now are important topics to think about. But this article does nothing to explore issues regarding these topics that are relevant today. Like how drug companies are patenting genes. Or how some biotech companies are trying to make designer seeds that won't reproduce. Or how insurance companies are already using medical information to discriminate and basically deny treatment, using the rudimentary genetic screening we know now. There are a lot of issues that are much closer than the fear of someone trying to design supermen. I say first things first.
But I don't think the point is to stop using antibiotics, anymore than we should stop genetic engineering, simply because bad things will happen. The point is that just because we can use them doesn't always mean we should, and that things we think of as A Good Thing aren't always.
And these are single-gene diseases, things that have very clear-cut phenotypes, things that we knew about long before the Project even started. Indeed, some of these things had already been sequenced. But how much more daunting would it be to try to come up with a genetic basis for things that we don't even have strict (or even vague, for that matter) biological/physical definitions for, like intelligence? I'm not saying it won't happen, but I think we'll have decades, if not centuries, to worry about it.
While cosmetic uses (as opposed to medical uses) for gene engineering will probably happen, it won't be the thrust of the technology, anymore than it is with surgery today. I'm pretty sure most scientists will be engrossed with solving existing problems before mucking around trying to create the "perfect baby." After all, if you had the money to fund a project, would you give money to something that would help your children but not yourself, or would you give money to something that would help you as well? And I really think it would be a one or the other situation, at least for now. Doing genetic engineering in somatic cells would be a lot different from doing it in germ cells.
Add to this the complication that the most pressing disorders are not of pure genetic origin, such as heart disease and cancer, and the idea of perfecting the human race simply through genetics becomes absurd. Heart disease has obvious environmental factors, and if you don't correct those, no amount of genetic engineering will save you. In fact, people without predispositions for heart disease can screw themselves over eating the wrong foods. And while some types of cancer have obvious hereditary components, all they do is set you up for the fall, like in retinoblastoma, Li Fraumeni's disease, or breast cancer. Environmental factors are the straws that break the camel's back--these are mainly light from the sun and oxygen, things you cannot avoid. Our DNA is being damaged every hour. It's just that most of these damaged cells are meant to die anyway, but sometimes you get unlucky. If you don't die of something else, if we somehow magically cure every other disease on the planet, you will die of cancer. The only way we can solve it is if we find a way to store genetic information in a more robust form than DNA--something science fiction writers like talking about. So while I'm not going to say it's impossible, that's certainly a long way off.
In addition, a lot of less common maladies are de novo mutations. While they can be inherited, a large number of cases just pretty much come out of thin air, from completely normal parents, conditions like neurofibramatosis and Down's Syndrome. In the case of Down's Syndrome, there is very little you can do about it in terms of raw sequence data. Someone will have to figure out why non-disjunction occurs with this chromosome so often--but even that's not that helpful because non-disjunction happens often with every chromosome. It's just that Down's Syndrome is the only one that is compatible with life. Everything else is spontaneously aborted, sometimes even without the mother knowing she was pregnant. So while maybe sequence info can help--we might figure out how certain sequences are important as binding sites in mitosis--sequence info will not be the sole answer. Some creative scientist will have to figure it out.
The idea of eugenics is pretty anathema to the current scientific mindset. Sure, there are some scientists out there who believe in it, but I really think that what we know is against them. As pessimistic as it sounds, I'm pretty sure Nature will figure out some way to kill us even if we somehow eliminated all disorders we know about now. Look at tuberculosis. We thought we had it licked, and now it's coming back. Look at HIV. Everything we throw at it just makes it stronger. Our drugs are in fact making it evolve into something less controllable.
Concern about insurance companies demanding sequence info, and discriminating on the basis of it is perhaps more relevant to current issues. Obviously, this is not going to happen very soon, considering that the human genome project is taking as long as it is. It is very unlikely that everyone will have to wait 10 years to get their sequence done and therefore get approved. But let's say we do figure out a way to do it in a more reasonable time frame. Well, this is nothing new--and I have issues with the existing system. Insurance companies already discriminate according to pre-existing conditions. Got diabetes? Too bad. Got thyroiditis? Oh well. How sequence info will make this better or worse is anybody's guess, but it's not going to turn us overnight into Aldous Huxley's Brave New World. Genetic screening already happens. People choose to abort fetuses that are "defective." Here's a novel case: an achondroplasic couple wanted an achondroplasic child, and wanted to abort it they had a normal child. But karyotypes for Down's are practically routine. I don't see us filing in line for soma just yet. (Or wait. Maybe that's what TV is...) I agree that the Human Genome Project and the ethics of what genetic engineering we are doing now are important topics to think about. But this article does nothing to explore issues regarding these topics that are relevant today. Like how drug companies are patenting genes. Or how some biotech companies are trying to make designer seeds that won't reproduce. Or how insurance companies are already using medical information to discriminate and basically deny treatment, using the rudimentary genetic screening we know now. There are a lot of issues that are much closer than the fear of someone trying to design supermen. I say first things first.
True. But apoptosis is basically a mechanism for cellular euthanasia, enacted in cells that would die anyway, or cause death in the whole organism if left unchecked. Failure of apoptosis can lead to such things like cancer, immune disease, and a host of other disorders. While cancer is cellular immortality, the whole organism will surely die.
Aging is a consequence of being in an oxidizing environment and being constantly bombarded by radiation, among other things. These things damage DNA, and the only reason we don't suffer more from it is exactly because of apoptosis.
Removing the program for apoptosis will probably do nothing to lengthen our lifespans. Neither will adding telomerase. Even organisms that don't have these things, like bacteria, succumb to entropy. It's simply statistically impossible to go on replicating DNA faithfully forever and expect to remain functional. Even with the multifarious repair mechanisms evolution has come up with, there is DNA damage. That's why evolution developed multiple, redundant chromosomes, sex, and apoptosis. Death is not a genetic constraint. It's simply physical.
Seriously, if you were a rich guy with a predisposition for cancer, would you fork over a ton of cash just so your kid wouldn't have cancer? Or would you rather fork over that ton of cash so that YOU wouldn't have cancer? I think that once the genome is complete, we'll probably spend more time treating existing conditions than doing cosmetic genetic engineering and designing the "perfect" human, because that's where the funding is going to be.
There are no genes that encode for aging or death. It is just a natural consequence of thermodynamics. Medical intervention will probably be more important than genetic intervention in determining our lifespans.
The funny thing is, this isn't a dead issue today. There IS a dilemma regarding the dispensation of antibiotics and antiseptics. They aren't unilaterally good. The overuse of antibiotics has generated drug resistant microorganisms that would never have existed otherwise.
I don't know too much about the brain, but it strikes me that the conclusion of the study doesn't really say anything about intelligence, or even anything about the correlation between profession and number of synapses, given how they measured the synapses. If they took brain tissue from an important part of the subjects' brain, wouldn't it affect the subjects drastically? If it isn't from an important part of the brain, then how can we be sure the finding has any meaning? Just because a certain neuron is being synapsed by a thousand axons doesn't mean that neuron is even being used. The fact that there are a lot of synapses might even demonstrate that that particular circuit isn't being used. We start out with more synapses prenatally then when we're adults. Then our connections are refined, so that a large number of these synapses are removed. This weeding out process is determined by the amount of electrical activity passing through a neuron. The multiplicity of synapses is part of the reason why we can't walk (or do much of anything) when we're born (that, and not having finished myelination.) Paring them down is what allows us to control our musculature. I realize brain synapses are drastically different from neuromuscular junctions, but I think the principle is the same. It's not the quantity, it's how they're connected that makes a big difference, not to mention the type of synapse they are.
Still, there are sequences that really do seem completely useless and can even have deleterious effects, like the Alu and L1 families of pseudogenes, which can replicate themselves autonomously, and randomly insert copies of themselves into the genome, on rare occasions breaking genes. There are around 500,000 copies of Alu in the genome, and about 10,000 copies of L1, for a total of 210 Mbp out of 3Gbp of total DNA. This dwarfs the estimated 120 Mbp of DNA that encodes proteins. And besides Alu and L1, there are tons of other pseudogenes scattered along the gene, essentially the cruft of evolution.
Thus, the junk is not necessarily useless, but neither is all the DNA necessarily useful. And of course it depends by what you mean as useful.