Posts
Comments
Here's a much better article criticizing evo-psych. I think it goes a little too far in some places, and I've posted it before, but those looking for something a bit more structured and well argued would do well to start here.
Yeah it doesn't say much. For one thing I'd say it's just about all of the genes that are differentially expressed, if you look hard enough. Regardless, that doesn't tell us how many of them really matter with respect to the things we care about, how many causal factors are at work, or how difficult it will be to fix. Doesn't rule out a single silver bullet aging cure (though other things probably do)
Yes that's the case. To get enough data we probably need lots of in vitro experiments. Remember that data is not equal to information - even really big sample sizes wouldn't be enough to resolve the combinatoric explosion. What I mean in that comment up there (I posted it before it was finished, I think) is that there are ~23k genes in the genome, so even under the absurdly simple assumption that there's only one mutation possible per gene, you have half a billion possible combinations of gene breakages, which you will never ever be able to get enough of a sample size to look at blindly.
Ha, in theory, but it looks like the guys at TeXmacs are already selling the product for free, so no dice...
Yes, that would also be great, but I a) I can't afford such a tablet, and b) I strongly suspect that the OCR would be inaccurate enough that I'd end up wishing for a keyboard anyway. Hell accurate voice recognition would be better, but I'm still waiting for that to happen...
Been using it for an hour now,and yes, it's crashed on me once, but no more than half the other programs I use. Already seeing the benefits of it when I spent half an hour doing something, realised there was a mistake at the start, and could then just find/replace stuff instead of scrunching the paper up into a ball and cursing Pierre Laplace. Also I don't have to deal with the aesthetic trauma of viewing my own handwriting. Outstanding.
YES. Thank you so much. Texmacs seems to be exactly what I wanted.
pen and paper is far more instant than any method I can imagine of poking mathematics in through a keyboard.
Yeah... I think I just have to bite this bullet. If you do math professionally and the people you know work onto pen and paper, then that's the answer.
It's just.... I feel like I can imagine a system that would be better than pen and paper. There's so much tedious repetition of symbols when I do algebra on paper, and inevitably while simplifying some big integral I write something wrong, and have to scratch it out, and the whole thing becomes a confusing mess. writing my verbal thoughts down with a keyboard is just as quick and intuitive as a pen and paper. There must be a better way...
Yeah I can imagine doing that all right - I wouldn't actually mind writing in latex even, the problem is the lag. Building a latex document after each change takes time. If the latex was being built in a window next to it, in real time, (say a 1 second lag would probably be fine) there'd be no problem. I'm not looking to publish the math, I just want a thought-aid.
Why isn't there a good way of doing symbolic math on a computer?
I want to brush up on my probability theory. I hate using a pen and paper, I lose them, they get damaged, and my handwriting is slow and messy.
In my mind I can envisage a simple symbolic math editor with keyboard shortcuts for common symbols, that would allow you to edit nice, neat latex style equations, as easily as I can edit text. Markdown would be acceptable as long as I can see the equation in it's pretty form next to it. This doesn't seem to exist. Python based symbolic math systems, like 'sagemath', are hopelessly clunky. Mathematica, although I can't afford it, doesn't seem to be what I want either. I want to be able to write math fast, to aid my thinking while proving theorems and doing problems from a textbook, not have the computer do the thinking for me. Latex equation editors I've seen are all similarly unwieldy - waiting 10 seconds for it to build the pdf document is totally disruptive to my thought process.
Why isn't this a solved problem? Is it just that nobody does this kind of thing on a computer? Do I have to overcome my hatred of dead tree media and buy a pencil sharpener?
I'm always puzzled by how many how many LWers seem to casually dismiss the reality of mortality with appeals to singularities, cryonics etc. I'm sure immortality is coming, but I don't see much chance of me living to see it. Seems prudent to come to terms with that.
See my answer on the other thread :) Difficult to estimate. You need a new method of transgenesis - 5-20 years?
Hmmmm. I'm shamefully ignorant about prices, but I would estimate such an effort would be in the tens of millions, if you wanted it done quickly (and it will still take a while). As far as I'm aware we haven't developed methods for transgenesis in Tetse flies, having only gotten the genome sequenced in 2014 (priorities people?!), and setting it up in a new organism in a new organism with an unusual life cycle can be surprisingly difficult. The link below describes techniques for manipulating gut microbes in the flies, which I don't think would suffice.
In drosophila you can't go from cell culture to an embryo easily like in mammals, you have to inject stuff into embryos and then breed from those embryos and hope some of your vector got into the germ line. In Tetse flies, I am now aware, the mother keeps the embryo until it's quite developed, meaning the techniques used in Drosophila wouldn't work, and we certainly don't have any tetse cell lines, which I doubt would be of use anyway. So you'd be looking at developing a novel means of transgenesis. (Viral vector targetting the germ line maybe?? ) Which is a task that, while no doubt solvable, inevitably has big uncertainties in it.
So yes, tens of millions, give or take an order of magnitude, plus years and years of work. Well worth doing though. In my opinion the potential gains far outweigh the risks.
P.S. The link to 'relevant risks' you posted is broken, I'd be interested in seeing it.
I'm totally in favor of chlorinating that pool, but just bear in mind that the 'registry of standard parts', and other biological tools in general, like CRISPR, are nowwhere near as easy to use and reliable as it says on the packaging. I'm always amused by the contrast between articles about CRISPR which make it sound like you can just jam a thumbdrive into a mouse, and the people I know trying to get CRISPR to work on a new cell line or organism, who are up all night for months in a row muttering schizophrenically in the cell culture room. You need a lot of time and human capitol for these things.
Another genomics PhD here. It's a complex topic. We know that combinatorial effects (epistasis in genetics lingo) matter, from population genetics studies in model organisms. This is despite the fact that simple linear models perform well in the human population - provided they are against some reasonably constant genetic background, low allele frequencies mean that the combinatorial effects are well captured by linear ones.
The problem is that even if you only care about pairwise combinations, there are far too many of them, given a uniform prior. Even if we sequence everyone on earth we wouldn't have anywhere near enough info, sequencing additional individuals has diminishing returns because there's only so much genetic variation in the human population (and ~23000^2 possible pairwise combinations).
What we need are good priors over combinations of mutations. To do that we'll need detailed info about which genes function together to produce which phenotypes. Such models exist already and are seeing moderate success, but we need new ideas and more data than any one startup could provide. Which is exactly what molecular biologists are working on.
Short answer - no, this is a hard, ongoing problem.
I think you're looking for the concept of 'mutational variance'. This is the amount of variation in a trait that is generated by random mutation. The variance in a trait is going to be determined by the balance of mutational variance and selective effects. Things with lots of genes effecting them will have a large 'mutational target size'. So for instance intellectual disability has a large mutational target size because there are so many different ways to break a brain, while some kinds of haemophilia have a large mutational target size because the particular sequences of DNA involved mutate a lot.
In general mutation variance is very difficult to measure outside of single celled organisms, although good approximations have been done in e.g. fruit flies. The problem is that it's very difficult to stop evolution from exerting it's filtering effect on your mutations before you can measure them.
So in the absence of direct measures, It's difficult to guess at how many genes might be involved in something like homosexuality, and what the mutational variance could be. On the surface, we can imagine it's just a simple trait that should have few genes effecting it. Such is the case in fruit flies. But actually, we just don't know enough about how evolution has created the human mind. Without knowing how genes produce a brain, we don't know enough to say that homosexuality isn't just a particularly common "failure mode" of the brain, like autism and ID. Maybe something about the way the human brain has evolved makes it turn out gay a lot.
Myself I don't really buy the 'gayness is selected for' explanations. My own opinion is that exclusive homosexuality might be more due to our own present society than anything else, and it's need to cordon off homosexual behaviour from normal, straight behaviour. If that's the case most of the mystery disappears.
WGS is going to get cheaper and cheaper as time goes on, presumably in the future we'll have developed a process for analysing the results properly. In the intervening time, there isn't much to be gained from it. SNP genotyping gives you most of the info about common variants, because the things it doesn't catch (deletions, insertions, etc.) will generally have some SNP in linkage to them. The rare variants are what you miss, and right now we don't really know what to do with them.
In general I wouldn't overestimate how much genotyping will tell you. Your family history is likely to be more informative.
I should be clearer on that score. It's not that I see a high likelihood of a singularity happening in the next 50 years, with Skynet waltzing in and solving everything. Rather I see new methods in Biology happening that render what I'm doing irrelevant, and my training not very useful. An example: lots of people in the 90s spent their entire PhDs sequencing single genes by hand. I feel like what I'm doing is the equivalent.
Cognitive genomics is definitely something I"ll look into, thanks.
Thank you, I'd never heard of Emerald Cloudlab. I guess I was speaking too much from my own observations and without enough research.
I don't mean to come across as super optimistic with respect to strong A.I., or even A.I. in general. I should have written '50 years give or take 50'. It's just that i think my field's progress rate is determined by the inflow of methods from other fields, and that the current problems it faces are insoluble using current ones. I think people who aren't immersed in the field get a mistaken impression about this because papers and press releases must communicate an artificial sense of progress and certainty to succeed. Word in the trenches is that we're mired in an intractable mess of unknowns.
As an example - take Aubrey de Grey's SENS program. He lays out all these alterations he thinks he can make to fix the problem of aging. But he seems to think of biology as modular and easily mutable. A biologist expects each individual step he proposes to face dozens of unforeseen problems, and to have many, many unpredictable knock-on effects, over a wide range of detectability and severity. Dealing with them all isn't doable right now, while single grad students take 5 year to determine a few of each genes many interactions and functions.
As for burnout - I'd agree with you if this was a recent development. But I've felt this way for years. It's just that now action is required. It's possible I've been burnt out for years. This has been suggested to me - my working environment is exceptionally poor - which is something I can say semi-objectively due to the number of people who have quit and/or echoed my feelings on the matter. I'm trying not to let those feelings influence me too much however.
This all hits the nail on the head I think. The marginal value of my PhD is, I'm convinced, at most zero, and perhaps negative, because it adds to the noise. The replicability of papers is significantly hindered by lack of automation, to my mind.
Also, saying that we don't know what 1/4 to 1/3 of human genes do is wildly optimistic. Better to say we have some idea what 2/3 of them do.
I have. I'm not wholly decided but as far as I can see the field suffers from most of the same problems that other biological fields do, and is also a bit overcrowded - research funding is pouring into it lately, and I think you could do more good by researching other fields that would feed them better methods, than by working in it directly.
I'd much rather learn C++ for all it's faults, since it meshes so nicely with R and Python, but people keep telling me to learn Java...
What I"m referring to in my field specifically is understanding gene regulatory networks. I've become convinced that the only way we're going to get a hold on them is by actually simulating the biochemistry. Searching for higher level abstractions within them just doesn't work that well. This will require lots and lots of experiments, which are currently done by hand, to be automated, and the results to be synthesized into very complex simulations. Humans are too slow, and their minds too small.
As for what I want, that's a good question. I'm not particularly enthusiastic about pouring our resources into tiny, high cost, low quality life extensions, which is what I see most of biology like cancer research, doing now (those parts of it that are aren't just furthering careers). I'd be more enthusiastic about improving quality of life for large numbers of people, or averting catastrophic risks.
Yes. I'm rather annoyed at myself for only now giving level 3 the kind of attention it deserves. Level 3 is hard though. Largely because other people can't help you as much. I'm kind of agnostic about what I want, to be honest. Nor do I have good information about my comparative advantages (due to relative ignorance of other fields) and the magnitudes of the trade offs to be made. Now is a time when I can take the time to think on and research these questions.
I'd estimate my altruism fluctuates between zero and ~70% on a daily basis, with a peak in the mornings immediately after get caffeinated.
These are all good points. And you're right that A.I. and robotics will come (for a while presumably) in the form of incremental improvements, as they already are.
I guess it feels to me though, like the rate of improvement is basically independent of biology itself, and is determined by the rate at which other fields hand it technology. Sequencing being a good example. We've basically done it to death now, and are waiting for someone to give us better methods that will yield new insights. The major bottleneck at the moment is that we insist on using grad students for manual labor, and nobody has the vision to see that the initial problems in automating basic laboratory tasks would be more than compensated for in the long run, as methods improve, provided there's a collective effort.
I'm also in general not enthusiastic about the many aspects of biology I see, because they seem aimed towards giving incremental life extensions to already affluent and long lived people, at great cost, or of helping a very small number of people at very high cost. Not that these aren't good goals, I just think there's lower hanging fruit.
Research (that I've seen) is in general patchy and inconsistent. But I take your point, it might be a frustrating enterprise. I think concentrating on a specific area is almost certainly a good idea.
This is the kind of 'I-wouldn't-have-thought-of-that' answer I was hoping for.
It would require substantial retraining, but this seems like a direction I could move in by choosing the appropriate post-doc, while also doing some useful work along the way. The general class of 'using biology to ensure the future occurs' contains a lot of potentially interesting things like plant biology and research involving things like salt and pathogen tolerant crops. Looks like I have some research to do :)
Jayman is correct that adoption studies typically show negligible parental effects. But remember the studies can only talk about the environmental variation present in their data, and are generally done on normal, western, middle class cohorts. In studies where they include stronger environmental variation - e.g. Turkheimer et al 2003, you find that it matters.
So basically, the kind of parenting choices that people typically worry about are probably meaningless, but severe trauma, poverty, abuse etc. do matter. That being said, You can't just say "X is difficult to encapsulate" with studies. This is a fully general counter argument to any evidence you don't like.
I'm a non-smoking vegetarian teetotaler who has to walk a kilometer between home and the bus stop. I hope that >counts.
Actually, in my experience, the amount of exercise needed for strong benefits to mood and energy is about 20 minutes hard exercise (talking during becomes difficult), at least 4 days per week. You could take up running. Murakami swears by it.
I don't have any suggestions for solving that, but I do think that as long as you hold that conflict it's going to be a big >obstacle to moving in any direction.
This. It may help to see you lack of security as a fair price payed for your career. Others experienced it early, you simply have to deal with it later on. People have overcome far worse. Start meditating.
Much sympathy. Your chosen career is a risky one and there probably isn't a way to make it safe - otherwise there would be even more writers than there are now. The way to avoid years of dread seems to me to have a good side job, one that leaves you with some energy to write. Some thoughts:
1) You may want to think about how you can overcome your disgust with all things economic - your parents poisoned that aspect of intellectual life, but economics is fairly well regarded here abouts - maybe you can salvage it for yourself by making it your own? Coming at it form a more LW perspective?
2) Can you just pull out from professional life? Start writing now, arrange to come in later, deliberately, so it doesn't become a guilt trip for you? Live cheaply and just start writing? It sounds like you've got plenty of frustrations and stuff to write about - why not just write it, as therapy if nothing else?
3) Do you need to prepare for the fact that you may simply not be able to be a writer? Everyone starts down that road without knowing if they can do it - it's a lottery. If I were you I'd try to confront that reality head on, and try to be process rather than results oriented.
4) Are you taking care of your life generally? Food, excersize, sleep? Generalized misery, for me, is usually about these things, rather than the causes - career, family etc., which my brain outputs when I ask it what's wrong.
Here here...
"I didn't have time to write you a short letter, so I wrote you a long one" I think the rapid part is in terms of the writer's time, not the readers'.
Yes, ignoring this advice was in retrospect very foolish. I badly underestimated how important the supervisor/student relationship is. I'm going to be a lot more careful next time.
Teaching is something I would love to do, but I was given to understand that you basically have to do research nowadays, due to the glut of academics.
There are a lot of things wrong, I don't know which of them is the most important...
1)I have zero control over my own work. I am working frantically all the time to complete analyses requested by other people, most of which turn out to be useless or ill thought out. People generally don't understand programming and stats enough to know how long things should take.
2)My boss is widely regarded as a bit of a tyrant. I have a powerful aversion to interacting with her in any way, and she has extremely poor communication skills. Our relationship is terrible. I think this is my fault as well, I work a lot but seem to get little done, and whenever I'm around her I feel a crushing sense of guilt and insecurity (this is all pretty melodramatic and childish - any my issue more than hers, but there it is).
3)The culture in my lab is about producing papers, not discovering things. I have the impression that almost none really give a crap about what we're studying.
4)I'm in a small town in a foreign country which I hate.
5)I have no belief in the value of the work we do. Nor do many of the smart people I've talked to. Many of these smart people have quit the lab recently. I was attracted to the lab by work that I didn't have skills to fully understand at the time. Knowing what i know now, I'd never have come. Our results take the form of vague correlations, and have no practical relevance to anyone.
6) Because I transferred into statistics from wet work a year into my PhD, my boss has been reluctant to give me any real responsibility. she's given me these vague, ill thought out side projects (other people's opinions, not my own), which has yielded dead end after dead end.
7) I generally have the impression that I am bad at my job. I have extreme difficultly focusing on my work and I make a lot of embarrassing bugs and errors. Part of this may be due to diagnosed attention difficulties, but I think most of it is just a total lack of interest. Forcing yourself to do something well when you don't care about it is difficult.
I think overall it's not so much the negative stuff as it is the total lack of positive reinforcement. Aside from a few brief false alarms, I have literally never had any success. I know there must be parts of the job that other people find rewarding, but i simply haven't experienced them.
I'm a year from completing a PhD in genomic science. I am now completely disillusioned with my field, and indeed professional life in general. I entered with ambition, and have been cleansed of it. I didn't quit early on because I lost all my self esteem and assumed the problem lay with me, and that I would be equally unhappy elsewhere. I'm now almost sure this is wrong, but I only have about a year to go, and no idea what to do next, and am fairly well paid, so quitting seems imprudent.
I have basic statistical and coding skills (whose usefullness in the real world I cannot assess) and honestly no idea what i want to do with my life. I cannot imagine enjoying a job anymore, but intellectually, I'm aware this is probably just a result of my present, rather toxic environment. I would like something socially valuable and/or lucrative, but will settle for something which has normal work hours and doesn't drain all the life out of me. My definition of socially valuable aligns well with that of the LW community, though I place much lower credence on a near term Singularity than most here, I think.
I imagine this is a common ish situation, and advice to me would be generally relevant.
1) Tell me if this is the wrong place for this kind of moaning 2) Advice? Sources thereof? Finding a job? Overcoming apathy? 3) How to assess the usefullness of ones skills? Low hanging ways of improving them?
That's a good point. I guess not. My intuition is that a lot of organisms have evolved simple multicellularity, and so would probably be doing better as unified multicellular organisms, but it's possible, as you say, that they haven't gotten to that point for lack of the niche. I don't know enough about the topic to say.
Yes. And this is what has happened to most branches of the tree of life. E.g. Archae Bacteria, the various Protists. Only very basic multicellularity occurs in most kingdoms.
Agree. the road from creation of life to creation of any nervous system at all is an extremely long and fraught one.
Life on our planet has a very specific chemistry. It's possible that almost all possible chemistries limit complexity more than ours - leading to many planets of very simple organisms. Very large number of phyla on earth reach evolutionary dead ends both archae and bacteria are stuck as single cellular organisms, (or very simple aggregrates) - Plants cannot develop movement because of their cell walls, while insects cannot grow bigger because their lungs and exoskeletons do not scale upwards.
Genetics is an entire optimization layer underlying our own, neural one. I think the fact that it had to throw up an entire new, viable optimization layer represents a filter.
I used to get these split second emotional flashbacks all the time, primarily when stressed. They were usually about embarrassing or frustrating moments, and would very frequently cause some kind of verbal twitch - usually these compulsive phrases like "I want to go home" or "I hate this place" or "I hate myself". Very embarassing in the rare instances it occured around other people.
Meditation seems to have brought down their frequency a lot. Or at least, of the many things that have changed, the frequency with which I meditate seems to correlate most closely.
I hate to sound machiavelian here, but i think an important criterion for a good sport missing from this discussion is "gain friends, respect, and a conversational topic with people who don't identify as rationalists".
A lot of us are going to be short on opportunities to achieve these goals. So the most instrumentally rational sport may be the one which happens to be popular in your immediate social environment.
Boxing is a great sport on almost all of the above criteria. Unfortunately, it's not an option for those with a preference for keeping their blood and their spinal fluid separate.
Also a chronic loser of keys. In addition to what's been suggested below - are your keys heavy enough? MIne have, e.g., a bottle opener and a usb key on them, and a very thick ring. The bottle opener in particular makes it difficult for them to slip out of a pocket, and the whole thing is heavy and noisy enough that a) it makes a lot of noise when dropped b) I can easily check for it's presence by patting my pants. Getting into the habit of doing this whenever leaving a location has saved me a lot of hassle.
Well done, but your link to the list of updated websites is broken.
though I am willing to accept an argument on statistical distributions and number of trials.
I would expect english media to just be better on average, due to the larger, more competitive market. Is this what you mean? (I imagine the foreign language/emotional reaction effect is the dominant thing going on though)
A modest proposal: Anyone wishing to create a file format will be forced to write out a 10 megabyte example of the format, by hand, without error, before the new format will be accepted.
If I had only had this advice at the beginning of my PhD, I would have saved myself a lot of hassle....
Also, the above advice would suggest, for instance, that we should use SAP's ridiculous, bloated crapware to manage human resources etc... Sometimes the multibillioner dollar companies fail.
One key meta mistake you see a LOT in computational biology is people not seeking out the proper expertise they need. I and countless other people have wasted months re inventing existing tools because I had no idea they existed, which is turn was because there were no experienced researchers around me with the relevant expertise to tell me.