I assume that you've never been a parent. (And neither have I, but you deal with a lot of parents in pediatrics, especially in the nursery. I admit, I've only been doing this for a few months, but bear with me....) I really don't think a baby's appearance is as commodifiable as the color of a car, or the size of your television screen. A lot of people (not just people of color) have a stake in having their children look like them. Otherwise, what's the point? Why have your own kids? Why not just have some other people's kids? (Not to mention the fact, how would you know that they even are your kids, if they don't look like you?)
Add to this the fact that the U.S. is (despite the separation of church and state) a pretty religious place (just listen to W the next time he has a press conference) and it makes me think that it is unlikely that everyone will whimsically change the characteristics of their kid just to conform. There are easier ways to conform, and to make your kids conform, than to muck around with DNA.
Finally, even if the technology is ubiquitous, you still have to make people go to these places and adhere to the regimens of genetic engineering. I mean, even today, ultrasound is ubiquitous, as are multivitamins, but you couldn't bribe some people into getting prenatal care, you could give them stuff for free, and they won't use it. And not necessarily because of any strong beliefs but sometimes because of sheer laziness, or different priorities (I mean, some people need to make money, instead of going to a doctor's appointment.) Imagine, these things that don't require invasive procedures, proven by scientific studies to give concrete advantages to newborns, often subsidized by the government, and people still say no.
That being said, I will not be at all surprised when designer babies are offered to the market. Yes, I agree, some people will absolutely jump at the chance. Probably the same people who get silicone implants and botox injections. Yes, vanity is pervasive in our consumerist culture, but it doesn't necessarily infect everyone.
I agree with you that genetic engineering has the potential to be available to everyone, in the same way that software development is available to anyone with a computer, but right now I am pessimistic. We haven't solved the problems of delivery yet, so we still need funding for R&D. And the amount needed to fund this hasn't declined to the point where venture capital alone will suffice. We're talking university support and NIH grants at the least. All the biotech companies in existence so far have pretty much merely spun-off research that was first discovered in a university lab. Breakthroughs still require massive capital, and, essentially, government subsidy.
Secondly, while in terms of physical space, you don't need much, you do still need to purchase some industrial equipment, like incubators and reagents and simple things like Erlenmeyer flasks and micropipets. Surely affordable for the average millionaire, but in this day and age, at least in the U.S., I can't imagine the Department of Homeland Security being too enthusiastic about anyone buying these things for their garage.
But then again, these R&D issues, and the complications of national defense, similarly cropped up in the history of software development as well. I'm sure that not many people in the '60s and '70s envisioned a world where everyone had a computer. For all I know, in a few decades, incubators for PCR the size of a desktop computer with built-in automated purification mechanisms will be just as ubiquitous.
Let's ignore the fact that the most important problem in genetic engineering today is delivery (i.e., how to get the modifications to enter the body and stay there) and while there have been a lot of exciting breakthroughs, the problem is far from solved.
While undoubtedly, all these growth factors will give benefits, like all substances, they have wonderful side effects. IGF has been linked to many types of cancer (although the mechanism is not understood) HGH will cause acromegaly and possibly (reading off the list of adverse reactions to Humatrope) leukemia, intracranial hemorrhage, and pancreatitis. And don't forget that, as mentioned in the article, the whole purpose of these factors is to promote cell division. And while cell division results in growth, it also increases the chances that some random error will occur and create an initiating mutation, eventually leading to malignancy.
Good luck with winning the Olympic gold medal when your body is riddled with sarcoma and you're getting chemo and radiation.
But this scenario already exists. People have been making fun and harassing people who are different since time immemorial. People have been discriminating against others who are genetic variants long before we even knew what DNA was. Just ask any person of color living in the U.S. (And ask any person of color whether they would be interested in giving birth to a blonde, blue-eyed child, too.)
Obviously not everyone will be able to afford getting modified. There will be billions of people who will go on reproducing without the benefit of gengineering, even in developed nations. Even if for some sick reason the government mandated that everyone had to be modified for the purposes of public health, the way that we mandate vaccinations now, how likely is it that absolutely everyone will comply? I think personal appearance, in the future, as it is now, will still be an indirect indicator of economic status.
Also, we are forgetting the enormous impact of environment. Despite having the technology to do so, we frequently fail to prevent in utero disease processes. (How much more likely are we going to have difficultly controlling every single complication that our modifications will introduce?) Imagine ordering the "perfect" DNA sequence for your child, only to have it scrambled by cytomegalovirus, which is as rampant as the common cold and just as preventable. Or when you have that Barbie child, and she gets a reaction from the chickenpox vaccine that many states are now mandating for all schoolchildren, she keeps scratching her lesions, and eventually develops scars. Or maybe she ends up surviving a building fire or a car crash. No amount of gengineering will easily reverse these appearance altering circumstances.
Umm, I'm pretty sure eukaryotes don't use restriction enzymes per se to manipulate DNA, unless you're using the term in a very broad sense. At least back when I was an undergrad, we only called things restriction enzymes if they recognized palindromic patterns in the nucleic acid sequence, and such things have thus far been only found in prokaryotes. So in theory, if the government decided to ban specific types of bacteria on the grounds that they could be used as biological weapons, the cost of restriction enzymes could be kept artificially high indefinitely, and it could become illegal to produce them.
But maybe it's even presumptious to think that creativity and language is at all encoded by a suite of 10,000 genes. While I'm not saying this is what the quoted scientist meant, the way the quote is presented makes it sound like you could just rip out that suite of genes and implant it into a pig, and now you've got a talking pig who can paint the ceiling of the Sistine Chapel.
While the "one gene equals one trait" model is a gross oversimplification that no one needs to argue about, I think the discussion has so far outlined what the real argument is about. I can guess that no one really fully believes either of the following extremes, but I think it does illustrate that there is a divide.
(1) Is the expression of the genome deterministic and programmatic, machine-like and concrete? That is, are the 10,000 genes, isolated from the rest of the genome, the sole basis of a particular characteristic, and once you've sequenced each gene and isolated each gene product, you can reconstruct the machinery of creativity and/or language? For example, maybe there are specific proteins that are localized only to Wernicke's area? Maybe the cytoarchitecture of the neurons in Broca's area are significantly different so that they have specific properties conducive to language? In this case, specific new gene products are expressed in specific parts of the organism, creating new structures (grossly or molecularly) that make certain traits possible. In this case, the genes themselves are paramount.
Or:
(2) Is the phenotype an emergent property that cannot be simplistically reverse engineered from its components. That is, are what we identify as "traits" something ephemeral and transient that cannot be pinpointed to specific molecules? That the new genes themselves don't code for anything concretely new, they are just another set of transcription factors that aren't significantly molecularly different from preexisting ones. In this case, there are no magic proteins that are necessary for creativity, there are no novel second messengers that generate language. Instead, the resultant increased complexity in the gene activation/inhibition cascades generates an altogether new behavior. A new pattern emerges from components that are molecularly identical, only perhaps the temporal pattern of expression has changed (possibly even due to changes in the environment--e.g., increased or decreased sunlight, changing the protein-to-carbohydrate ratio of food ingested, a billion other things that don't have anything to do with genes per se), or since there are more agents interacting, existing interactions generate different behavior. But knowledge of how many helix-turn-helix motifs are in the new factors or how many leucine zippers will not necessarily elucidate what these gene products create. In other words, the genes themselves don't necessarily matter, it is only the new interactions that do.
Like I said, these are artificial distinctions, since in some cases, the former is true, in other cases the latter is true, but in most cases, both are true at the same time. But philosophically speaking, I think it makes a great difference in how you approach the problem experimentally.
With the Asimov reference, I assume you are bringing up the speculation that life could've easily been based on D-amino acids instead of L-amino acids, except that for some unknown reason one dominated the other. (Kind of like the speculation that we could exist in a universe made mostly off anti-matter instead of matter, except for some strange inequality present during the Big Bang.) Here I agree.
But perhaps what the writer meant to say is that, given that life as we know it started off with a particular handedness, and the machinery of the Central Dogma is composed of right-handed DNA and proteins made up of L-amino acids, it would require less energy to continue using L-amino acids than trying to incorporate D-amino acids... hence the self-perpetuating inequality. Not that D-amino acids aren't ever incorporated (as in bacterial cell walls).
I haven't read anything specifically about this, but is the chirality of the amino acids used in protein synthesis at all related to the fact that the DNA molecules they are ultimately synthesized from have a handedness to them as well? (As DNA is usually in the B-form, which is right handed) I realize that there is an mRNA intermediate before actual translation, but wouldn't the enzymes that handle transcription need to have a particular handedness to process DNA?
Teleogical, I know, but what we see now is perhaps, again, the end result of the fact that (1) While RNA was probably the original genetic material, DNA is a more efficient, less error-prone way to package code, so DNA eventually dominated (i.e., replicated faster) (2) DNA has a preferential handedness simply because of basic chemistry. The left handed Z-form is not as stable as the right handed B-form. (3) While both RNA and DNA can spontaneously form base pairs if sitting in a sea full of nucleotides, and while RNA can act like an enzyme, replication happens much faster if you can recruit proteins. Somehow DNA (and probably RNA before it) preferentially chemically bound to certain amino acids/peptides/proteins, and the machinery of the Central Dogma appeared after a billion or so years of chemical "trial and error". (4) Since DNA has a particular handedness, the proteins that handle it mostly have a certain handedness as well. (5) This handedness is derived from the fact that these proteins are composed of amino acids of a uniform chirality.
Heh, you can take Fragmin prophylactically--this is what they usually do for patients in the hospital who have to be immobilized and I hear that some people actually do this before they go on trans-Pacific flights. There are also TED hose (anti-embolism stockings) and SCDs (sequential compression devices: basically a pneumatic sleeve that wraps around your leg, which a machine pressurizes every so often to help blood move back to the heart)
But unfortunately, it doesn't really matter if you are productive. No matter how much work you do while sitting, if you don't move your legs for long periods of time, you are at risk for DVTs. And if you're in front of a computer, unless you're playing Dance Dance Revolution, you're probably not moving your legs very much.
You only need to monitor APTT with unfractionated heparin (because of the variability of bioavailability). Because low molecular weight heparin is more predictable, you can get away with not monitoring APTT. The only reason you would take heparin and warfarin at the same time is when they are weaning you off of heparin and starting you on warfarin. The rationale for preferring warfarin is that it can be taken by mouth, whereas you have to inject heparin. The reason they don't give warfarin from the onset is that it takes a while for it to kick in, so they start with heparin. Greenfield (inferior vena cava) filters are usually reserved for cases when warfarin and heparin are both contraindicated (which is usually because you are bleeding from somewhere else like, for example, your brain) Greenfields aren't that great for life-long treatment because they eventually get blocked up and might actually become a source of clots, and usually need to be removed after a couple of years. If you have recurrent DVTs or pulmonary emboli, you usually have to be on warfarin for the rest of your life. Surgical removal of clots is rarely done unless the clot is so huge that it's impinging on nearby structures like nerves or other blood vessels, or when a massive one blocks the main artery that supplies the lungs (although this has an 80% mortality rate even if they do open you up)
Notable side effects of heparin: thrombocytopenia (in rare cases, heparin actually will destroy your platelets) Notable side effects of warfarin: skin necrosis, where large patches of skin turn black. Of course, either of these two can cause you to bleed massively. Luckily, they are reversible: unfractionated heparin with protamine sulfate, low molecular weight heparin with Factor X, and warfarin with Vitamin K.
It is not so much what the brain does, but the mis-callibration of the dampening mechanisms that happen *before* brain processing that is the concern being expressed.
But my point (which btw is well expressed by "The Matrix") is that anything before brain processing is irrelevant. As someone pointed out in another thread, you can train your brain to see upside things right side up and then train it back to normal, with no damage. So any miscalibration can always be corrected by succeeding inputs. But the thing is, it is the brain that decides what is important and what is extraneous, and what I'm trying to say is that most brains don't care about whatever lossy compression cuts out anyway.
I don't know. Generally training that is *harder* than reality is a better skill builder than easier/simpler. Worf did not battle bunny rabbits on the holedek.
This is not really true. Notice you mention the holodeck, which by definition is easier than reality. You don't have to deal with actually being killed. The way most people practice skills, whether it is playing the violin, doing an appendectomy, or learning how to fight with a Klingon Bat'leth, is to start easy, and to build upon that. Once simple skills become automatic, it is easier to learn more complicated skills. This does not work very well in reverse. Just because you learn a complicated skill from the start does not mean you can perform, much less understand, the simple skills that it is built upon.
Even if the premise of the article is true, I actually think that the filtering out of unsensed stimuli is a good thing when it comes to hearing, and in fact, to all senses.
The whole challenge of decoding sensory input is not so much in trying to sense every little variation in the environment, but more in finding meaningful patterns in the input. The way the brain processes information is inherently lossy anyway. For example, the brain does not store the direct input from your retina. There is no bitmap of RGB values of every image that you've ever laid eyes on. What remains in the brain are only the connections to other processing centers, such as the limbic system which controls emotion or the parietal lobes which guide spatial perception, which get reinforced every time a similar input presents itself. And it seems that all the senses work this way.
If anything, the way codecs emphasize a pattern (e.g., a song) helps reinforce the particular tracts in the neural wiring that recognize this pattern. In fact, in the article, it is even pointed out that the whole reason the feedback tracts (i.e., the efferent fibers that run back to the cochlea) exist is precisely to dampen out unwanted input, so that the desired sensory pattern can be better recognized.
(Hence, e.g., the ability to hear a conversation 10 feet away despite being in a roaring crowd at a stadium)
And in any case, hearing did not evolve for us to be able to enjoy music. Compared to other species, our auditory acuity generally sucks, and these limitations are hardwired into our genetics. Instead, in a sense, music evolved precisely because of the way we hear. Our brains are good at finding patterns in seemingly random streams of information and listening to music, which is definitely less random than ambient environmental noise even out in the wilderness of precivilization, may very well continually reinforce this ability. In other words, input that is simpler than what naturally occurs in reality reinforce tracts in our brain that help us pick out the same inputs in challenging, distracting environments.
The Hardy-Weinberg equilibrium is only an ideal case. The answers derived from the equation are not meant to be exact, but they tend to be good enough, so much so that in epidemiology, the five assumptions of no mutation, no gene flow, no genetic drift, random mating, and no natural selection can be used as a starting point for calculating incidence and prevalence even when there is obvious data that contradicts the five assumptions. Given that most mutations are lethal, and most of the remainder are silent, the mutation rate doesn't factor into the equation all that much--the mutation rate only matters if the mutations are non-lethal and therefore actually change the gene pool. While gene flow may affect human subpopulations, it doesn't really matter for the human race as a whole because we are all stuck on this planet for the time being. And because of globalization and the current ease of travel due to airplanes, genetic drift isn't all that important either. Only non-random breeding and natural selection are likely to influence the equation in this case, and since there is unlikely to be hard data at this point, I would hazard to guess that despite various anecdotes, red haired people really aren't selected as mates more often than anyone else, and while one might infer from this story that there is a different survival rate for being red-haired vs. not, I'd be willing to bet that the selective pressure is miniscule at best.
Heh, maybe this ultimately proves that the basic sciences aren't as useful as clinical, hands-on experience. While my med school is the same--I have plenty of classmates who never went to lecture their M1 and M2 years--you can fail an entire rotation by just missing one day at the hospital or clinic unless you have a really, really good reason.
Not actually true. All AAMC accredited med schools require hands-on clinical patient contact for 3rd and 4th years, most schools introduce it in the 2nd year, and a good number even start in 1st year. 3rd and 4th year are when you do your clerkships (more commonly called "rotations")--the scope of your responsibilities tend to depend on the site you're at. It can be as inane as simply following a resident physician around, or it can be as demanding as actually completely managing the patient, requiring an attending physician only to sign the prescriptions and the chart.
Right now I am doing my Emergency Medicine rotation at Cook County Hospital right now (which serves as the facade for E.R. the show; the insides are radically different to say the least) and while all the people in white coats may be performing like physicians, a good number of us are just 3rd and 4th year med students.
To actually become a physician requires a lot more than just reading out of books. For one thing, a good chunk of what you need to know isn't even written in books yet--some things only exist in the minds of clinicians, and for another thing, as many of my preceptors are wont to say, patients don't really read the textbooks, and for another thing there's no way to learn procedures without actually doing them.
How then do you explain so-called reperfusion injury, which is definitely a real phenomenon on the gross level? Current molecular explanations revolve around either the idea that once apoptosis is initiated, it is irreversible, or the idea that the restoration of blood flow and hence oxygen supply actually adds fuel to the flames by creating even more free radicals AKA reactive oxygen species. Most likely, it is some combination of both, and even though control of apoptosis will not completely stop such injuries, it could at least reduce it and thereby change the outcomes of patients who have strokes or heart attacks.
I agree, apoptosis and necrosis due to oxidation are not the same thing, but if you agree with the current elucidated mechanisms, they are not unrelated.
The point that they have in common is alteration of mitochondrial membrane permeability. In apoptosis, different signal transduction cascades (initiated by factors such as FasL found on cytotoxic T cells that can therefore kill virus-infected or tumor cells, TNF [tumor necrosis factor] secreted by macrophages in inflammation, and tumor suppresor genes like p53 and Rb which initiate apoptosis after sensing DNA damage) affect the balance between pro-apoptotic proteins (e.g. Bax and Bad) and anti-apoptotic proteins (e.g. Bcl-2 and Bcl-XL). (These proteins are analogs of the ced gene products found in C. elegans) If the pro-apoptotic proteins win out, mitochondrial membrane permeability is altered, cytochrome c gets dumped into the cytosol (essentially stopping ATP production), and the caspases (which are also proteins that are analogs of the ced gene products) are activated and proceed to effectively dismantle the cell. Similarly, oxidation of the cell membrane alters cell permeability, causing, among other things, a massive influx of calcium, which in turn also alters mitochondrial membrane permeability, once again dumping cytochrome c into the cytosol and activating caspases.
Another way that oxidation is linked to apoptosis is that free radicals damage DNA. The damaged DNA is sensed by products of tumor suppressor genes such as p53 and Rb, and apoptosis is initiated.
In most cases of pathological cell death, both necrosis (which is essentially the unregulated death of a cell due to loss of membrane integrity, inadvertant release of destructive enzymes, and destruction of critical regulatory proteins) and apoptosis (which is by contrast exquisitely regulated) are occurring simultaneously.
And while telomerase serves an interesting purpose in regulating the cell cycle, it is by no means the only cause of aging. Most of the pathology of aging is caused by mechanical and structural damage to cells: the accumulation of intracellular debris, wear and tear on the cytoskeleton, damage to the genome. While free radicals aren't the only factors that cause this damage, they undoubtedly do have a significant effect.
Telomerase is only important in cells that continue to divide, but the organ systems that are most affected by aging are typically populated by cells that don't really reproduce at all or at least reproduce very infrequently, such as neurons in the brain and myocytes in the heart.
What I wish the article had discussed is how thymic transplants would actually help in treating HIV infection or in preventing transplant rejection.
Since T cells are initially generated in the bone marrow, a new thymus wouldn't have much of an effect with increasing T cell populations. Furthermore, even if you could somehow boost T cell numbers, what's to prevent the virus from infecting these new cells?
With organ transplantation, reject happens most rapidly when HLA haplotypes between donor and recipient aren't perfectly matched, and a new thymus wouldn't really do much to solve this mismatch.
On the other hand, I can easily see how this new development can help children with SCIDs or congenital thymic hypoplasia/aplasia.
The thymus is only really necessary for the maturation of T cells which takes place in early life. T cells are actually continuously produced by stem cells in the bone marrow. Once mature, T cells generally reside in the peripheral blood and in lymph nodes. While the thymus does secrete cytokines that promote lymphoid proliferation, there are other organs/tissue types like lymph nodes and bone marrow that can also supply the necessary substances.
The new thymus won't necessarily affect existing immunity, as mature T cells hang out in the blood. (And immunity normally wears off anyway since T cells have finite life spans.) The bigger problem is that, unless the stem cells from which the new thymus are derived from are perfect HLA matches with the existing immune system, graft vs. host disease is likely to occur.
There are at least three types of T cells: Th cells (helper T cells), Tc cells (cytotoxic T cells), and TDTH cells (delayed-type hypersensitivity T cells). The existence of Ts cells (suppressor T cells) has been postulated but is apparently still controversial. In addition, Th cells are further subdivided into Th1 cells necesary for cell-mediated immunity (primarily targeting viral infections and tumors) and Th2 cells necessary for antibody production. T cells and B cells are both lymphocytes, which are a different lineage of white blood cells than macrophages.
The 21st amino acid, selenocysteine, while rare, is actually integral in synthesizing important eukaryotic enzymes like glutathione peroxidase (necessary for the stability of red blood cells) and 5'-deiodinase (necessary for regulating thyroid function).
What is remarkable about selenocysteine and pyrrolysine is that they are actually encoded by the genome. This is in contrast to hydroxyproline and hydroxylysine (and gamma-carboxyglutamate, necessary for blood clotting) which are encoded by standard proline, lysine, and glutamate codons. It's not until the peptides are being modified in the endoplasmic reticulum and Golgi apparatus that the hydroxy- or carboxy- groups are added on.
While we don't really know why the genetic code is for the most part universal, it's probably dictated by thermodynamics and natural selection. The 20 amino acids we have are all pretty much readily synthesized from glucose--pretty much the common fuel for all life--and its metabolites. So ultimately this would limit the different permutations of carbon atoms.
And while the genetic code is pretty universal, mitochondria use a slightly modified version, and according to the article, Salmonella have tRNAs that recognize four bases instead of just three.
The short explanation for why only L-amino acids are found (except in bacterial cell walls) is that all the enzymes required for translation (and for the most part, all enzymes in general) are stereospecific--the substrate has to fit in the binding cleft the same way only your left hand can really fit into a left glove.
As for why only certain R groups are found, it's probably ultimately dictated by thermodynamics, with a little input from natural selection. Nature is very conservative with the building blocks it uses, and almost all of the amino acids used can be derived from glucose and its various metabolites. n>2 alkanes R groups would probably require a lot of energy to synthesize, particularly since they're hydrophobic and all these reactions happen in an aqueous environment. If you can't make it from glucose within the thermodynamic constraints of a biological system, you're unlikely to make it.
Probably because of thermodynamics as well, not all codons occur with equal probability. And because of the thermodynamic instability of the third base pair with regards to codons/anti-codons binding, many tRNAs are only specific for the first two bases (a phenomenon known as "wobble")
Because of thermodynamic and steric considerations, it would be difficult for ribosomes to accept dipeptide/tripeptide tRNAs, since the active sites on the enzymes have only so much leeway as to where they expect to physically find the atoms they're supposed to act on. While theoretically an alternate translation system could evolve, given the conservative nature of evolution, it would probably take a long time and require severe selective pressure.
Finally, as for "junk" DNA, a lot of it has been found to serve various structural functions with regards to the integrity of the genome. There are probably very few regions of even heterochromatin that don't have a function, and the sequences that are truly useless now probably had a function in the evolutionary past.
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Add to this the fact that the U.S. is (despite the separation of church and state) a pretty religious place (just listen to W the next time he has a press conference) and it makes me think that it is unlikely that everyone will whimsically change the characteristics of their kid just to conform. There are easier ways to conform, and to make your kids conform, than to muck around with DNA.
Finally, even if the technology is ubiquitous, you still have to make people go to these places and adhere to the regimens of genetic engineering. I mean, even today, ultrasound is ubiquitous, as are multivitamins, but you couldn't bribe some people into getting prenatal care, you could give them stuff for free, and they won't use it. And not necessarily because of any strong beliefs but sometimes because of sheer laziness, or different priorities (I mean, some people need to make money, instead of going to a doctor's appointment.) Imagine, these things that don't require invasive procedures, proven by scientific studies to give concrete advantages to newborns, often subsidized by the government, and people still say no.
That being said, I will not be at all surprised when designer babies are offered to the market. Yes, I agree, some people will absolutely jump at the chance. Probably the same people who get silicone implants and botox injections. Yes, vanity is pervasive in our consumerist culture, but it doesn't necessarily infect everyone.
Secondly, while in terms of physical space, you don't need much, you do still need to purchase some industrial equipment, like incubators and reagents and simple things like Erlenmeyer flasks and micropipets. Surely affordable for the average millionaire, but in this day and age, at least in the U.S., I can't imagine the Department of Homeland Security being too enthusiastic about anyone buying these things for their garage.
But then again, these R&D issues, and the complications of national defense, similarly cropped up in the history of software development as well. I'm sure that not many people in the '60s and '70s envisioned a world where everyone had a computer. For all I know, in a few decades, incubators for PCR the size of a desktop computer with built-in automated purification mechanisms will be just as ubiquitous.
While undoubtedly, all these growth factors will give benefits, like all substances, they have wonderful side effects. IGF has been linked to many types of cancer (although the mechanism is not understood) HGH will cause acromegaly and possibly (reading off the list of adverse reactions to Humatrope) leukemia, intracranial hemorrhage, and pancreatitis. And don't forget that, as mentioned in the article, the whole purpose of these factors is to promote cell division. And while cell division results in growth, it also increases the chances that some random error will occur and create an initiating mutation, eventually leading to malignancy.
Good luck with winning the Olympic gold medal when your body is riddled with sarcoma and you're getting chemo and radiation.
Obviously not everyone will be able to afford getting modified. There will be billions of people who will go on reproducing without the benefit of gengineering, even in developed nations. Even if for some sick reason the government mandated that everyone had to be modified for the purposes of public health, the way that we mandate vaccinations now, how likely is it that absolutely everyone will comply? I think personal appearance, in the future, as it is now, will still be an indirect indicator of economic status.
Also, we are forgetting the enormous impact of environment. Despite having the technology to do so, we frequently fail to prevent in utero disease processes. (How much more likely are we going to have difficultly controlling every single complication that our modifications will introduce?) Imagine ordering the "perfect" DNA sequence for your child, only to have it scrambled by cytomegalovirus, which is as rampant as the common cold and just as preventable. Or when you have that Barbie child, and she gets a reaction from the chickenpox vaccine that many states are now mandating for all schoolchildren, she keeps scratching her lesions, and eventually develops scars. Or maybe she ends up surviving a building fire or a car crash. No amount of gengineering will easily reverse these appearance altering circumstances.
Umm, I'm pretty sure eukaryotes don't use restriction enzymes per se to manipulate DNA, unless you're using the term in a very broad sense. At least back when I was an undergrad, we only called things restriction enzymes if they recognized palindromic patterns in the nucleic acid sequence, and such things have thus far been only found in prokaryotes. So in theory, if the government decided to ban specific types of bacteria on the grounds that they could be used as biological weapons, the cost of restriction enzymes could be kept artificially high indefinitely, and it could become illegal to produce them.
While the "one gene equals one trait" model is a gross oversimplification that no one needs to argue about, I think the discussion has so far outlined what the real argument is about. I can guess that no one really fully believes either of the following extremes, but I think it does illustrate that there is a divide.
(1) Is the expression of the genome deterministic and programmatic, machine-like and concrete? That is, are the 10,000 genes, isolated from the rest of the genome, the sole basis of a particular characteristic, and once you've sequenced each gene and isolated each gene product, you can reconstruct the machinery of creativity and/or language? For example, maybe there are specific proteins that are localized only to Wernicke's area? Maybe the cytoarchitecture of the neurons in Broca's area are significantly different so that they have specific properties conducive to language? In this case, specific new gene products are expressed in specific parts of the organism, creating new structures (grossly or molecularly) that make certain traits possible. In this case, the genes themselves are paramount.
Or:
(2) Is the phenotype an emergent property that cannot be simplistically reverse engineered from its components. That is, are what we identify as "traits" something ephemeral and transient that cannot be pinpointed to specific molecules? That the new genes themselves don't code for anything concretely new, they are just another set of transcription factors that aren't significantly molecularly different from preexisting ones. In this case, there are no magic proteins that are necessary for creativity, there are no novel second messengers that generate language. Instead, the resultant increased complexity in the gene activation/inhibition cascades generates an altogether new behavior. A new pattern emerges from components that are molecularly identical, only perhaps the temporal pattern of expression has changed (possibly even due to changes in the environment--e.g., increased or decreased sunlight, changing the protein-to-carbohydrate ratio of food ingested, a billion other things that don't have anything to do with genes per se), or since there are more agents interacting, existing interactions generate different behavior. But knowledge of how many helix-turn-helix motifs are in the new factors or how many leucine zippers will not necessarily elucidate what these gene products create. In other words, the genes themselves don't necessarily matter, it is only the new interactions that do.
Like I said, these are artificial distinctions, since in some cases, the former is true, in other cases the latter is true, but in most cases, both are true at the same time. But philosophically speaking, I think it makes a great difference in how you approach the problem experimentally.
But perhaps what the writer meant to say is that, given that life as we know it started off with a particular handedness, and the machinery of the Central Dogma is composed of right-handed DNA and proteins made up of L-amino acids, it would require less energy to continue using L-amino acids than trying to incorporate D-amino acids... hence the self-perpetuating inequality. Not that D-amino acids aren't ever incorporated (as in bacterial cell walls).
Teleogical, I know, but what we see now is perhaps, again, the end result of the fact that (1) While RNA was probably the original genetic material, DNA is a more efficient, less error-prone way to package code, so DNA eventually dominated (i.e., replicated faster) (2) DNA has a preferential handedness simply because of basic chemistry. The left handed Z-form is not as stable as the right handed B-form. (3) While both RNA and DNA can spontaneously form base pairs if sitting in a sea full of nucleotides, and while RNA can act like an enzyme, replication happens much faster if you can recruit proteins. Somehow DNA (and probably RNA before it) preferentially chemically bound to certain amino acids/peptides/proteins, and the machinery of the Central Dogma appeared after a billion or so years of chemical "trial and error". (4) Since DNA has a particular handedness, the proteins that handle it mostly have a certain handedness as well. (5) This handedness is derived from the fact that these proteins are composed of amino acids of a uniform chirality.
Maybe?
Heh, you can take Fragmin prophylactically--this is what they usually do for patients in the hospital who have to be immobilized and I hear that some people actually do this before they go on trans-Pacific flights. There are also TED hose (anti-embolism stockings) and SCDs (sequential compression devices: basically a pneumatic sleeve that wraps around your leg, which a machine pressurizes every so often to help blood move back to the heart)
But unfortunately, it doesn't really matter if you are productive. No matter how much work you do while sitting, if you don't move your legs for long periods of time, you are at risk for DVTs. And if you're in front of a computer, unless you're playing Dance Dance Revolution, you're probably not moving your legs very much.
Notable side effects of heparin: thrombocytopenia (in rare cases, heparin actually will destroy your platelets) Notable side effects of warfarin: skin necrosis, where large patches of skin turn black. Of course, either of these two can cause you to bleed massively. Luckily, they are reversible: unfractionated heparin with protamine sulfate, low molecular weight heparin with Factor X, and warfarin with Vitamin K.
But my point (which btw is well expressed by "The Matrix") is that anything before brain processing is irrelevant. As someone pointed out in another thread, you can train your brain to see upside things right side up and then train it back to normal, with no damage. So any miscalibration can always be corrected by succeeding inputs. But the thing is, it is the brain that decides what is important and what is extraneous, and what I'm trying to say is that most brains don't care about whatever lossy compression cuts out anyway.
I don't know. Generally training that is *harder* than reality is a better skill builder than easier/simpler. Worf did not battle bunny rabbits on the holedek.
This is not really true. Notice you mention the holodeck, which by definition is easier than reality. You don't have to deal with actually being killed. The way most people practice skills, whether it is playing the violin, doing an appendectomy, or learning how to fight with a Klingon Bat'leth, is to start easy, and to build upon that. Once simple skills become automatic, it is easier to learn more complicated skills. This does not work very well in reverse. Just because you learn a complicated skill from the start does not mean you can perform, much less understand, the simple skills that it is built upon.
The whole challenge of decoding sensory input is not so much in trying to sense every little variation in the environment, but more in finding meaningful patterns in the input. The way the brain processes information is inherently lossy anyway. For example, the brain does not store the direct input from your retina. There is no bitmap of RGB values of every image that you've ever laid eyes on. What remains in the brain are only the connections to other processing centers, such as the limbic system which controls emotion or the parietal lobes which guide spatial perception, which get reinforced every time a similar input presents itself. And it seems that all the senses work this way.
If anything, the way codecs emphasize a pattern (e.g., a song) helps reinforce the particular tracts in the neural wiring that recognize this pattern. In fact, in the article, it is even pointed out that the whole reason the feedback tracts (i.e., the efferent fibers that run back to the cochlea) exist is precisely to dampen out unwanted input, so that the desired sensory pattern can be better recognized. (Hence, e.g., the ability to hear a conversation 10 feet away despite being in a roaring crowd at a stadium)
And in any case, hearing did not evolve for us to be able to enjoy music. Compared to other species, our auditory acuity generally sucks, and these limitations are hardwired into our genetics. Instead, in a sense, music evolved precisely because of the way we hear. Our brains are good at finding patterns in seemingly random streams of information and listening to music, which is definitely less random than ambient environmental noise even out in the wilderness of precivilization, may very well continually reinforce this ability. In other words, input that is simpler than what naturally occurs in reality reinforce tracts in our brain that help us pick out the same inputs in challenging, distracting environments.
The Hardy-Weinberg equilibrium is only an ideal case. The answers derived from the equation are not meant to be exact, but they tend to be good enough, so much so that in epidemiology, the five assumptions of no mutation, no gene flow, no genetic drift, random mating, and no natural selection can be used as a starting point for calculating incidence and prevalence even when there is obvious data that contradicts the five assumptions. Given that most mutations are lethal, and most of the remainder are silent, the mutation rate doesn't factor into the equation all that much--the mutation rate only matters if the mutations are non-lethal and therefore actually change the gene pool. While gene flow may affect human subpopulations, it doesn't really matter for the human race as a whole because we are all stuck on this planet for the time being. And because of globalization and the current ease of travel due to airplanes, genetic drift isn't all that important either. Only non-random breeding and natural selection are likely to influence the equation in this case, and since there is unlikely to be hard data at this point, I would hazard to guess that despite various anecdotes, red haired people really aren't selected as mates more often than anyone else, and while one might infer from this story that there is a different survival rate for being red-haired vs. not, I'd be willing to bet that the selective pressure is miniscule at best.
Heh, maybe this ultimately proves that the basic sciences aren't as useful as clinical, hands-on experience. While my med school is the same--I have plenty of classmates who never went to lecture their M1 and M2 years--you can fail an entire rotation by just missing one day at the hospital or clinic unless you have a really, really good reason.
Not actually true. All AAMC accredited med schools require hands-on clinical patient contact for 3rd and 4th years, most schools introduce it in the 2nd year, and a good number even start in 1st year. 3rd and 4th year are when you do your clerkships (more commonly called "rotations")--the scope of your responsibilities tend to depend on the site you're at. It can be as inane as simply following a resident physician around, or it can be as demanding as actually completely managing the patient, requiring an attending physician only to sign the prescriptions and the chart.
Right now I am doing my Emergency Medicine rotation at Cook County Hospital right now (which serves as the facade for E.R. the show; the insides are radically different to say the least) and while all the people in white coats may be performing like physicians, a good number of us are just 3rd and 4th year med students.
To actually become a physician requires a lot more than just reading out of books. For one thing, a good chunk of what you need to know isn't even written in books yet--some things only exist in the minds of clinicians, and for another thing, as many of my preceptors are wont to say, patients don't really read the textbooks, and for another thing there's no way to learn procedures without actually doing them.
How then do you explain so-called reperfusion injury, which is definitely a real phenomenon on the gross level? Current molecular explanations revolve around either the idea that once apoptosis is initiated, it is irreversible, or the idea that the restoration of blood flow and hence oxygen supply actually adds fuel to the flames by creating even more free radicals AKA reactive oxygen species. Most likely, it is some combination of both, and even though control of apoptosis will not completely stop such injuries, it could at least reduce it and thereby change the outcomes of patients who have strokes or heart attacks.
I agree, apoptosis and necrosis due to oxidation are not the same thing, but if you agree with the current elucidated mechanisms, they are not unrelated.
The point that they have in common is alteration of mitochondrial membrane permeability. In apoptosis, different signal transduction cascades (initiated by factors such as FasL found on cytotoxic T cells that can therefore kill virus-infected or tumor cells, TNF [tumor necrosis factor] secreted by macrophages in inflammation, and tumor suppresor genes like p53 and Rb which initiate apoptosis after sensing DNA damage) affect the balance between pro-apoptotic proteins (e.g. Bax and Bad) and anti-apoptotic proteins (e.g. Bcl-2 and Bcl-XL). (These proteins are analogs of the ced gene products found in C. elegans) If the pro-apoptotic proteins win out, mitochondrial membrane permeability is altered, cytochrome c gets dumped into the cytosol (essentially stopping ATP production), and the caspases (which are also proteins that are analogs of the ced gene products) are activated and proceed to effectively dismantle the cell. Similarly, oxidation of the cell membrane alters cell permeability, causing, among other things, a massive influx of calcium, which in turn also alters mitochondrial membrane permeability, once again dumping cytochrome c into the cytosol and activating caspases.
Another way that oxidation is linked to apoptosis is that free radicals damage DNA. The damaged DNA is sensed by products of tumor suppressor genes such as p53 and Rb, and apoptosis is initiated.
In most cases of pathological cell death, both necrosis (which is essentially the unregulated death of a cell due to loss of membrane integrity, inadvertant release of destructive enzymes, and destruction of critical regulatory proteins) and apoptosis (which is by contrast exquisitely regulated) are occurring simultaneously.
And while telomerase serves an interesting purpose in regulating the cell cycle, it is by no means the only cause of aging. Most of the pathology of aging is caused by mechanical and structural damage to cells: the accumulation of intracellular debris, wear and tear on the cytoskeleton, damage to the genome. While free radicals aren't the only factors that cause this damage, they undoubtedly do have a significant effect.
Telomerase is only important in cells that continue to divide, but the organ systems that are most affected by aging are typically populated by cells that don't really reproduce at all or at least reproduce very infrequently, such as neurons in the brain and myocytes in the heart.
What I wish the article had discussed is how thymic transplants would actually help in treating HIV infection or in preventing transplant rejection.
Since T cells are initially generated in the bone marrow, a new thymus wouldn't have much of an effect with increasing T cell populations. Furthermore, even if you could somehow boost T cell numbers, what's to prevent the virus from infecting these new cells?
With organ transplantation, reject happens most rapidly when HLA haplotypes between donor and recipient aren't perfectly matched, and a new thymus wouldn't really do much to solve this mismatch.
On the other hand, I can easily see how this new development can help children with SCIDs or congenital thymic hypoplasia/aplasia.
The thymus is only really necessary for the maturation of T cells which takes place in early life. T cells are actually continuously produced by stem cells in the bone marrow. Once mature, T cells generally reside in the peripheral blood and in lymph nodes. While the thymus does secrete cytokines that promote lymphoid proliferation, there are other organs/tissue types like lymph nodes and bone marrow that can also supply the necessary substances.
The new thymus won't necessarily affect existing immunity, as mature T cells hang out in the blood. (And immunity normally wears off anyway since T cells have finite life spans.) The bigger problem is that, unless the stem cells from which the new thymus are derived from are perfect HLA matches with the existing immune system, graft vs. host disease is likely to occur.
There are at least three types of T cells: Th cells (helper T cells), Tc cells (cytotoxic T cells), and TDTH cells (delayed-type hypersensitivity T cells). The existence of Ts cells (suppressor T cells) has been postulated but is apparently still controversial. In addition, Th cells are further subdivided into Th1 cells necesary for cell-mediated immunity (primarily targeting viral infections and tumors) and Th2 cells necessary for antibody production. T cells and B cells are both lymphocytes, which are a different lineage of white blood cells than macrophages.
What is remarkable about selenocysteine and pyrrolysine is that they are actually encoded by the genome. This is in contrast to hydroxyproline and hydroxylysine (and gamma-carboxyglutamate, necessary for blood clotting) which are encoded by standard proline, lysine, and glutamate codons. It's not until the peptides are being modified in the endoplasmic reticulum and Golgi apparatus that the hydroxy- or carboxy- groups are added on.
And while the genetic code is pretty universal, mitochondria use a slightly modified version, and according to the article, Salmonella have tRNAs that recognize four bases instead of just three.
As for why only certain R groups are found, it's probably ultimately dictated by thermodynamics, with a little input from natural selection. Nature is very conservative with the building blocks it uses, and almost all of the amino acids used can be derived from glucose and its various metabolites. n>2 alkanes R groups would probably require a lot of energy to synthesize, particularly since they're hydrophobic and all these reactions happen in an aqueous environment. If you can't make it from glucose within the thermodynamic constraints of a biological system, you're unlikely to make it.
Probably because of thermodynamics as well, not all codons occur with equal probability. And because of the thermodynamic instability of the third base pair with regards to codons/anti-codons binding, many tRNAs are only specific for the first two bases (a phenomenon known as "wobble")
Because of thermodynamic and steric considerations, it would be difficult for ribosomes to accept dipeptide/tripeptide tRNAs, since the active sites on the enzymes have only so much leeway as to where they expect to physically find the atoms they're supposed to act on. While theoretically an alternate translation system could evolve, given the conservative nature of evolution, it would probably take a long time and require severe selective pressure.
Finally, as for "junk" DNA, a lot of it has been found to serve various structural functions with regards to the integrity of the genome. There are probably very few regions of even heterochromatin that don't have a function, and the sequences that are truly useless now probably had a function in the evolutionary past.