[HN Gopher] New CRISPR-based map ties every human gene to its fu...
___________________________________________________________________
New CRISPR-based map ties every human gene to its function
Author : gumby
Score : 448 points
Date : 2022-06-10 15:54 UTC (1 days ago)
(HTM) web link (news.mit.edu)
(TXT) w3m dump (news.mit.edu)
| loxias wrote:
| > New CRISPR-based map ties every human gene to its function
|
| The title would be so much better if s/its/a/.
|
| There is no way we'll have an operative map from "all" genes to
| function anytime soon. Sometimes hundreds of genes work together,
| interact with other microbiomes we contain or our environment to
| produce what might seem to be a "simple" quality like height.
| ngcc_hk wrote:
| Very frightening ... good to know relativity but then we have
| nuclear bomb. Not sure the negative side to this. Just hope the
| good side out win any bad use of information about all of us.
| achenet wrote:
| There's an interview with Ken Thompson from about 2008 where he
| says that most of the work in CS has already been done, and he's
| advising his son to go into biology.
|
| I feel like CRISPR is the transistor of the 21st century.
| dekhn wrote:
| CRISPR is more like a machine to make large-node-size
| integrated circuits. Somebody else has to design the circuit,
| make it manufacturable, and integrate the circuit with a whole
| bunch of other hardware.
|
| I work in biotech at a company that is one of the few golden
| geese that lays 2-3 successful drugs with no competitors every
| few years. I have 30+ years of experience (deep experience) in
| machine learning, biology, and computer science.
|
| We are so far behind where we could be, in terms of turning
| biology into technology, that's almost shameful. Every day I
| see another system that says it can generate 10 times the data
| of the previous machine, but the actual amount of knowledge we
| are extracting for all that data collection is growing
| logarithmically. This is because for a long time biology has
| greatly underfunded computing and data.
|
| The one great shining light is AlphaFold. AF2 finally
| demonstrated to a wide range of scientists across many domains
| that a really great team using techniques that are barely known
| outside of FAAMG can work with some long-term experts to move a
| metric (quality of predicted protein structures compared to
| golden data) substantially further and faster than even the
| most wildly optimistic predicted. Not only that, some of the
| techniques they used didn't even exist several years ago
| (transformers, jax, various graph learning systems), and the
| work was replicated externally once the leading academic team
| had a hint of the direction to go in.
|
| To me, nothing about what I said is surprising to me; I
| predicted these outcomes a long time ago. Most of the reasons
| that it comes slower than it could are combinations of culture,
| incentive, morals/ethics, politics, innovator's dilemmas and a
| hundred different bottlenecks. Recently, the challenge has been
| that most of the really smart computational biologists
| disappear into FAAMG and don't contribute back the things they
| learn there to research.
|
| We're all waiting for that next moment when the cross product
| of Genentech and Isomorphic Labs announces that they have a
| computational model that can do end to end prediction of drug,
| from initial disease target to FDA approval post-phase III
| trial. That's been the dream for some time but we're nowhere
| near it still, and it remains to be seen whether some group can
| conjure all the necessary bits to solve the remaining
| underlying problems associated with that "far beyond NP-hard
| problem"
| printf42 wrote:
| Shouldn't it be MAANG now?
| OJFord wrote:
| It's long since named a concept rather than a specific set
| of companies, nobody cares (or intends to mean) what it
| actually stands for.
| mannymanman wrote:
| Are there any low-hanging fruit in biology in your opinion?
| Or will most important problems take a while to solve?
| Invictus0 wrote:
| AI?
| JKCalhoun wrote:
| Perhaps also future biology?
| jazzyjackson wrote:
| I'm still holding out for photonics and other optical-analog
| computers (where are my instantaneous trig co-processors?) but
| that does sound like good advice
| foobiekr wrote:
| The problem with this is that biology will likely end up
| dominated by China due to a willingness to conduct experiments
| that are otherwise non-viable in most countries.
| jeffreyrogers wrote:
| There's still so much basic research to be done that I doubt
| this will be a limiting factor for a while.
| ornornor wrote:
| > non-viable
|
| Did you mean unethical or are you talking about something
| else?
| mod wrote:
| Forbidden by law or fear of backlash (often due to ethical
| implications)
| seydor wrote:
| Biology is being automated by startups that are doing the
| experiments for you, AWS-style. Looks like software is going to
| be eating biology as well
| mannymanman wrote:
| any examples?
| kyawzazaw wrote:
| Radix.bio
| jarenmf wrote:
| Yeah, it feels like most fields are stagnated except for
| biology and neuroscience. I am a postdoc right now but have
| considered seriously switching fields to work on something
| exciting.
| PartiallyTyped wrote:
| I fail to see how CS has stagnated since 2008, so I hope
| somebody could illuminate it for me.
| shimon wrote:
| I studied CS and now work in software systems for biomedical
| research. It's difficult to overstate how different the fields
| are, so I don't entirely agree with this statement. But I do
| agree there are going to be lots and lots of huge discoveries
| in biology in the 21st century.
|
| The main difference is that CS attempts to generate and study
| complex systems built from well-understood components, whereas
| biology attempts to understand and manipulate systems that
| evolved naturally over eons.
|
| Imagine dropping a fully functional internet-connected Google
| Home Hub into 1960-era humanity and asking them to figure out
| how it works so they modify it to sound like Walter Cronkite.
| There are thousands of problems on this order of complexity in
| biology. It's wild.
| tyre wrote:
| think of the tech debt in our legacy codebase
| elevaet wrote:
| 3.7 billion years of refactoring has kept it pretty clean
| and functional. We'll need to do a shit ton of unit and
| integration testing before we commit changes.
| redtexture wrote:
| There is a lot of pruning that occurs, evolutionarily
| speaking, and a lot of what was thought to be "useless"
| genome has been discovered to be conserved over
| generations, and that there is use for that part of the
| genome.
| pddpro wrote:
| How difficult is it to transition from Computer Science to
| Biomedics? Particularly towards the field of Genomics (where
| CRISPR is).
| Balgair wrote:
| Having done the physics -> neuro leap, it's pretty tough.
|
| You have to learn a whole new set of fields and new ways of
| thinking. That takes time. To be 'good' at genomics, you
| kinda need to know how the genes are implemented in the
| various model organisms. Which means you need to know the
| relevant biology, biochemistry, chemistry, and physics of
| the situations. That's, essentially, an entire undergrad
| education. Then, you get to do the actual work, which takes
| about 1.5 years of study, so most of a masters degree. Then
| you can start really doing the work.
|
| For me, the first big realization coming from physics was
| that these little yeast cells and zebrafish aren't just
| little machines of quantum chemistry. They really are
| alive, even down to the cellular level, and they are
| studying _you_ too. There were hundreds of such insights.
| mannymanman wrote:
| What was your path going from CS -> bio? Interested in a
| similar path
| pddpro wrote:
| Same here. The more I've progressed in CS, the more
| dissatisfied I am. Outside of creating algorithms that vie
| for constant user attention (the basic business model of
| FAANG), I don't see any fruitful application of my skills.
| I'd much rather move towards the domains where my knowledge
| of data, systems, and algorithms could be better utilized
| (medicine, Genomics, structural engineering, governance
| etc).
| Balgair wrote:
| I've done the physics->neuro leap, so I may be of some
| use here.
|
| The path is pretty clear, but takes time. Essentially,
| you need to go back to school and learn biology.
|
| Fortunately, many grad programs in the US are desperate
| for people that want to be trained as biologists but have
| relevant skills in other areas like CS. So skip going
| back to undergrad and just apply to grad programs.
|
| Unfortunately, that means you have to join the Ivory
| Tower's horrible system for a while. A 'good' tactic is
| to get into a PhD program where you'll be paid, learn
| everything, get your MS, and then quit the program after
| ~3 years with a free MS. Fair warning, the learning will
| be absolutely horrible and you'll be on the bubble of
| being kicked out; it really is that much info you're
| trying to digest in such a short time period. But if
| you're not worried about scholarships and grades, then
| that's fine. Your PI will hate you, but then again they
| hate everyone, so it's a wash.
|
| If you're serious about grad school then read this first:
| https://acoup.blog/2021/10/01/collections-so-you-want-to-
| go-...
|
| One thing to be clear about though, jobs in biotech are
| much less well paid than in CS. You're looking at a 1/3rd
| to 1/4th salary decrease for pure bio jobs as compared to
| programmer jobs. Even leveraging your coding skills for
| biotech companies is going to be tough; you'll be pigeon
| holed into either a lab role or a coder role. The true
| blended roles are very rare. So much so as that you'll
| essentially have to start your own company, or be the
| heart of any company your join. So, good money there, but
| huge pressures.
| jazzyjackson wrote:
| This is basically chaos engineering applied the the genome
|
| It doesn't say "this gene has this outcome" so much as it says
| "this outcome fails when this byte of data is missing"
| throwawaycities wrote:
| About 18-24months ago I went through a phase of listening to
| geneticists talks/conferences/podcasts for an hour or two a day
| during long runs, it's so far outside my wheelhouse I'm
| probably mixing things up, but I thought I recalled cutting
| edge experiments using synthetic cells to create artificial
| life (a worm perhaps with a relatively simple DNA, maybe even a
| modified DNA further simplifying the genome to the furthest
| extent possible still resulting in life) with one of the goals
| of understanding the exact functions of all the genes in this
| "simple" DNA. Again I'm probably mixing up multiple discussions
| and studies into one, but I would have been very surprised if
| the function of every single gene in the human genome was known
| and understood, as suggested by the title.
| tablespoon wrote:
| > I recalled cutting edge experiments using synthetic cells
| to create artificial life (a worm perhaps with a relatively
| simple DNA, maybe even a modified DNA further simplifying the
| genome to the furthest extent possible still resulting in
| life)
|
| A worm seems super-complex for something like that. I'd guess
| they'd actually use a bacterium.
| dekhn wrote:
| I worked with mycoplasma genitalium which is a "minimal"
| organism- an extremely small number of genes, nearly all of
| which appear to be absolutely required for viability. It's
| sort of a unit test for model biology, except it grows so
| slowly it's more like an integration test in terms of
| performance.
|
| You are probably referring to Mycoplasma genitalium JCVI-1.0
| ( (see https://en.wikipedia.org/wiki/Mycoplasma_genitalium)
| as worms are too complex to be minimialized
|
| See also
| https://en.wikipedia.org/wiki/Mycoplasma_laboratorium
|
| The work in this area is quite extraordinary, but typically
| gets much less attention than _anything_ that works with
| human genomes.
| gilleain wrote:
| Hmm wonder how Craig Venter is getting along with his
| project. He was making a lot of noise about it a few years
| ago.
|
| Seems like he sold a company in April of this year to the
| University of California.
| lgas wrote:
| Maybe https://en.wikipedia.org/wiki/Caenorhabditis_elegans#
| Use_as_... ?
| dekhn wrote:
| c. elegans is much more complicated. It has the advantage
| of eutely, but it's awfully complex for minimalist
| studies.
| throwawaycities wrote:
| Thank you for the comment and the link.
|
| This expert from the first link is very likely what I was
| poorly trying to regurgitate:
|
| > Mgen still has the smallest genome of any known
| (naturally occurring) self-replicating organism and thus is
| often the organism of choice in minimal genome research.
| The synthetic genome of Mgen named Mycoplasma genitalium
| JCVI-1.0 (after the research centre, J. Craig Venter
| Institute, where it was synthesised) was produced in 2008,
| becoming the first organism with a synthetic genome.
|
| > The work in this area is quite extraordinary, but
| typically gets much less attention than anything that works
| with human genomes.
|
| In fairness laymen like me would just get us all mixed up
| with a worm genome anyway ;). In my defense I'm just a
| lawyer that likes to listen to foreign topics I find
| interesting while I run, but it is nice to confirm I have
| good instincts, because I really did find this work to be
| extraordinary and fascinating.
| girfan wrote:
| Can you please share pointers to some of the podcasts etc.
| you listened to? Looking for something similar for non-Bio
| expert people.
| mariebks wrote:
| Can you link to some of your favorite
| talks/conferences/podcasts? Thanks!
| throwawaycities wrote:
| I wish I could be more helpful, but this was during a
| period I was distance running everyday for years without
| much concern on what I was consuming so long as I found it
| interesting.
|
| In terms of popular podcasts maybe I could say Lex
| Friedman, but then I might search for one of his guests, or
| specific topics I wanted to learn more about, on YouTube
| and look for lectures or panel discussions in the results
| that looked like they might be high quality.
| bigbillheck wrote:
| "This Week in Virology": https://www.microbe.tv and sister
| podcasts.
| yellowcake0 wrote:
| Well, depending on how broad your definition of life is,
| viruses have the most stripped down genomes of all. In the
| smallest viruses, with genomes of just under 10kb in length,
| nearly every basepair is dedicated to either infection or
| replication. In fact, they are often so compact that open
| reading frames are interleaved, in order to provide more
| functionality without increasing size.
|
| Scientists often refer to viruses as "obligate", in order to
| sidestep the question of what is life, as most have no
| interest in the topics which occupy philosophers. In any
| case, they are non-cell based, for whatever that is worth. I
| imagine in a non-hostile environment, even the infection
| functional would be shed, and you would be left with just
| replication, which is the fundamental component beyond which
| no further reduction in complexity can be made.
| bigbillheck wrote:
| > viruses have the most stripped down genomes of all
|
| Giant viruses can have over 1M basepairs, substantially
| larger than a bacteria such as Mycoplasma genitalium, with
| substantial functionality (pretty much everything except
| the ribosome in at least some of them:
| https://www.virology.ws/2018/03/08/only-the-ribosome-is-
| lack...)
| afterburner wrote:
| > I imagine in a non-hostile environment, even the
| infection functional would be shed, and you would be left
| with just replication
|
| A virus replicates by infecting another cell and taking
| over its actual replication infrastructure, so getting rid
| of infection gets rid of replication too.
| ethbr0 wrote:
| Minimal genome -
| https://en.m.wikipedia.org/wiki/Minimal_genome
|
| I thought some work on it made HN, but can't seem to find the
| article, about a research group that was continuing to strip
| things out and then test viability.
| yellowcake0 wrote:
| You may also be interested in the Yeast 2.0 project,
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894084/
|
| which is an attempt to redesign the genome of the model
| organism S. cerevisiae, i.e. standardize codons, remove junk
| DNA, etc.
| [deleted]
| pishpash wrote:
| It's kind of a dead end I feel. It can turn out that everything
| is used for everything. It's not designed so there is probably
| no clean decomposition nor is it necessary.
| david_l_lin wrote:
| Not really?
|
| It says that some genes result in the same outcome when knocked
| out as other genes, and identifies novel genes that putatively
| participate in the same pathways as others. This helps get at
| the potential function of genes without known functions.
| jazzyjackson wrote:
| > It says that some genes result in the same outcome when
| knocked out as other genes
|
| a very useful map to make, but I don't see that this
| contradicts my comment - both genes in this case are
| dependencies to the outcome, without either of them, the
| outcome fails
|
| this does not sound to me like we know the "function" of
| these genes, only that they're nessary for each phenotype
|
| not to knock the research, just trying to make sense of what
| they're really mapping, in my own language of computer code
| (i suppose "function" has a different connotation in
| genetics)
| david_l_lin wrote:
| > "this outcome fails when this byte of data is missing"
|
| The outcomes here are not failures, they are measurable
| phenotypic differences, which they use to group genes into
| phenotypic outcomes. The typical "knockout -> failure to
| perform a function" is not what's being measured here.
| timy2shoes wrote:
| > this does not sound to me like we know the "function" of
| these genes, only that they're nessary for each phenotype
|
| But they're not even measuring the phenotype. They're using
| the transciptional signature as a substitute for
| phenotype/cell function (i.e. the bag of RNA model). This
| is a poor substitute if you try to apply this to practical
| applications such as cell engineering. Let's say I perturb
| a cell to match it's transcriptional signature to that of a
| neuron. Does that make it a neuron? Not if it doesn't
| function like a neuron.
| twic wrote:
| I think this is a really important point. With a few
| exceptions (like the neat implied aneuploidy assay), they
| haven't measured an outcome or phenotype for the genes.
| They have measured the impact on transcription (well,
| mRNA levels, via transcription or some other effect).
| That is an extremely useful dataset, but it's not enough
| to say what the phenotypic effect of knocking out any
| given gene is, much less what the actual mechanistic
| function of the gene product is.
|
| It's also important to note that there are loads of genes
| whose effects are not mediated by changes in mRNA levels.
| If you knock out Arp2, a cell can't move properly,
| because Arp2 is involved in assembling cytoskeletal
| structures needed to do that, but you probably won't be
| able to tell that by looking at the cell's mRNA.
| dekhn wrote:
| So, people do this a lot and frequently make mistakes. For
| example, when you knock out a gene, you also damage any
| overlapping genes (yes, genes can overlap). most studies
| don't pay attention to the damage they do to overlapping
| genes.
|
| The underlying physical model for how gene products interact
| to make phenotypes ends up being so hopelessly complex and
| latent that most conclusions in this area end up being
| "sufficient, but not necessary" instead of "necessary, but
| not sufficient"
| ramraj07 wrote:
| Not sure if you're doing it a service or disservice calling it
| chaos engineering: at best it's related. If you want to figure
| out what a complex system does where you have no ability to
| "see", the only tool you have most of the time is to knock out
| individual components and see what happens.
|
| As you might guess this is generally a blunt tool which can
| help you get to the first 30% of the understanding of the
| system but minimal extra data after that. The majority of genes
| discovered in this study would either be already known players
| in those pathways or unknown genes that would already have been
| guessed to play a role.
|
| Until one of these massive screens tells us what the major
| vault protein complex does they should all be honest about what
| they are which Imo is just a minor addition.
| Victerius wrote:
| Designer babies incoming.
|
| Turn off the genes that would make my child below 6'5 in
| adulthood, turn off the genes that wouldn't make him naturally
| muscular, turn off the genes that would give him an average
| intelligence, etc.
|
| $10M + options. Payable in monthly installments.
| zen_1 wrote:
| Turn on the Myostatin inhibitors!
| WitCanStain wrote:
| A new genetic aristocracy. Great.
| elif wrote:
| Yea human culture will find a new level of 'basic' combined
| with an inferred and understood if not blatantly codified
| position of social superiority... Sounds more like twilight
| zone than social progress to me.
| cronix wrote:
| What do you think they would choose if they had the option
| for gender, orientation and sexual preference?
| Victerius wrote:
| Most wealthy couples with the means to afford designer
| babies would probably want heterosexual children. Gender
| would be left at their discretion.
| mcculley wrote:
| Not just wealthy couples. Most parents want their
| children to be heterosexual and bear them grandchildren.
| Having successfully procreated, they are more likely to
| have natalist genes and inclinations.
| lajamerr wrote:
| Why would they need to be heterosexual to successfully
| procreate.
|
| If the future is designer babies/baby incubation pods. It
| doesn't matter what sexual orientation the kid is. The
| parent would have a designer baby, then why would the
| child eventually not have a designer baby as well?
| DrudgeCorporate wrote:
| You will always need an Egg or Sperm depending on which
| is missing in the relationship. Also, one of the parents
| would not have genetic code in the offspring since you
| can't splice two eggs/sperm together as far as I know.
| inglor_cz wrote:
| In Vitro Gametogenesis has been improving lately. 20
| years from now, making an egg from a stem cell harvested
| from a male might be possible.
| blamestross wrote:
| We already selectively breed for natalists and look how
| that turns out. It actually makes an argument that
| genetic predisposition to natalism is currently rather
| weak and it is mostly memetic predisposition in practice.
| InitialLastName wrote:
| The demographic trends we're seeing now (declining birth
| rates for affluent people in the developed world) could
| be due to our natalism level being mis-calibrated for our
| current circumstances.
|
| It's good evolutionary strategy to reduce the birth rate
| to compensate for successful reproduction (i.e. more
| pregnancies that result in offspring that reach child-
| rearing age themselves), as otherwise populations will
| explode beyond the carrying capacity of the environment
| (or pay more of the fixed resource costs of raising
| children than is necessary).
|
| What we see now, however, is that in situations where
| both pre-adult and maternal mortality rates are
| _exceedingly_ low (such as has been the case for the last
| ~4-5 generations in the developed world), the strategy
| undershoots the replacement rate.
| fgkramer wrote:
| We just need to see Gattaca to be horrified at the results of
| such experiment.
| sneak wrote:
| I have seen Gattaca and don't find human genetic
| engineering to be horrific. It's cool and exciting that
| people will be able to have better children than they would
| have otherwise.
| tablespoon wrote:
| > I have seen Gattaca and don't find human genetic
| engineering to be horrific. It's cool and exciting that
| people will be able to have better children than they
| would have otherwise.
|
| Did you even pay attention to the movie? The horrific
| aspect was the human genetic engineering led 1) to the
| the _un_ engineered to be turned into an underclass that
| was blatantly and unfairly discriminated against, and 2)
| that same discrimination would be turned against the
| engineered if they had an accident that caused them to
| fall short of the expected perfection.
|
| I have little doubt that the reality of genetic
| engineering (that was is effective as that depicted)
| would rhyme with that movie. It's also nearly certain
| that any such technology would not be distributed in an
| egalitarian way, so the sentiment should be more like
| "it's cool and exciting that [well off] people will be
| able to have [genetically superior] children than [the
| plebs]."
| sneak wrote:
| We have underclasses based on genetics now. Let's not
| pretend mate selection on Earth in 2022 is a meritocracy.
| It's mostly just racism, a slower form of deliberate
| genetic engineering of one's offspring.
|
| If anything, this would increase the amount of
| opportunity in the world, as then your child could have
| whatever traits you (or your culture) deems superior. It
| would perhaps eliminate racism by rendering traditional
| race markers completely obsolete.
| o_____________o wrote:
| I understood the intention of the movie, but I'm also in
| the camp that thinks engineering ourselves is the way
| forward, and a given. Genetic and silicon advances have a
| real potential to make us super/transhuman and immortal.
|
| > It's also nearly certain that any such technology would
| not be distributed in an egalitarian way
|
| This argument could have been made about early computers
| as well. But time and its economies of scale come into
| play. We can't limit our species based on shortsighted
| fairness, there's a longer view to take.
| tablespoon wrote:
| > I understood the intention of the movie, but I'm also
| in the camp that thinks engineering ourselves is the way
| forward, and a given. Genetic and silicon advances have a
| real potential to make us super/transhuman and immortal.
|
| Techno-optimism hasn't really panned out as promised.
|
| And I really doubt it will be "us." If trans-humanism
| pans out (though I suspect it's bunk), we'll be the Homo
| erectus populations to their Homo sapiens.
|
| > This argument could have been made about early
| computers as well. But time and its economies of scale
| come into play. We can't limit our species based on
| shortsighted fairness, there's a longer view to take.
|
| Capital got automation from computers, the plebs got
| distraction boxes that push ads.
| o_____________o wrote:
| This response would have been perfect if you had signed
| off with "Sent from my iPhone"
| tablespoon wrote:
| > This response would have been perfect if you had signed
| off with "Sent from my iPhone"
|
| Because it's a distraction box or _so_ amazing that it
| shows technology should not be criticized and everyone
| who does is a hypocrite?
| LargoLasskhyfv wrote:
| Hrm. So what? How is that different from the uneven
| distribution of
| money/wealth/power/medicine/upbringing/private
| schools/university/"connectedness" today?
|
| This will be just another currency. And there will be
| some flops, busts, unintended consequences. Just like
| with anything else.
|
| _Ist mir scheissegal!_
| tablespoon wrote:
| > Hrm. So what? How is that different from the uneven
| distribution of
| money/wealth/power/medicine/upbringing/private
| schools/university/"connectedness" today?
|
| Vague resemblance does not an equivalency make.
|
| Right now, there may be an unequal distribution of
| wealth, etc.; but the wealthy by and large aren't
| actually better models of human. Genetic engineering has
| the potential to ossify that (both morally via
| "meritocracy" and physically) with biological
| superiority. It stops being Homo sapiens vs Homo sapiens,
| and becomes something more like Homo erectus vs Homo
| sapiens.
| o_____________o wrote:
| People will balk at this, which is funny in contrast to
| how much human energy is poured into ego, signaling and
| mate selection as proxies for perpetuating favorable
| genetics.
| nescioquid wrote:
| > It's cool and exciting that people will be able to have
| better children than they would have otherwise.
|
| You know, I used to be wary of eugenics, but when you put
| in that light, yeah, I'm kinda tired of putting up with
| everyone's crap kids. If you could make them be quiet,
| sit still, and do as told, that would be a fantastic
| achievement! Oh, and maybe make them smarter, too. Ever
| try to actually _talk_ to one (the newer ones are really
| pretty stupid)?
| sneak wrote:
| Genetic engineering of one's own children is not
| eugenics. It's not even close.
|
| Most of my friends' children are smart. The ones not
| raised in the USA are generally well-behaved. Your sample
| size may need to be increased.
| donkarma wrote:
| civilized wrote:
| It's embarrassing when self-appointed "bioethicists" do
| _nothing_ but handwring about distant transformative
| technology - stuff that could confer such incredible benefits
| on humanity and that we are light-years from having.
|
| It's so _easy_ for them to posture as virtuous protectors of
| humanity, sowing FUD about things that are so far from
| existing that nobody even understands how they might work or
| what capabilities they might have or not have. So easy, when
| the benefits are nowhere near close enough to factor into
| anyone 's near-mode thinking.
|
| I'm cheering for the scientists. Give us the choice to have
| brilliant, strong, healthy children. Then laugh at how little
| anyone cares about the so-called "ethics", facile cloud-talk
| that never considered real people facing real decisions.
|
| The "ethicists" had their chance to intelligently weigh the
| pros and cons and give real advice based in prudence,
| empathy, and a love for human flourishing. They chose to
| self-indulgently chinstroke about dystopia on the taxpayer
| dime.
|
| We'll figure it out without them.
| hooande wrote:
| This is how I feel about AGI
| rowanG077 wrote:
| Honestly I love this future. There are so many bad traits
| humans have that would help everyone a great deal if they
| would be eliminated.
| elif wrote:
| Consider that idea's other subscribers in history, the ones
| utilizing that exact rationality... Are you in good
| company?
| rowanG077 wrote:
| I think so. Alexander Graham Bell, Helen Keller, Winston
| Churchill, Plato and there are countless more. Just
| because we didn't have the technology to implement it
| humanely in the past doesn't mean it can't be done in the
| future.
|
| In fact. I would consider a society, that has the
| capability to noninvasively eliminate for example sickle
| cell anemia or Huntingtons and doesn't because some
| people one hundred years ago did horrible things,
| barbaric.
| Emma_Goldman wrote:
| Churchill had some virtues of leadership, but he was an
| abominable racist and colonialist, even by the standards
| of his time.
|
| >"Churchill is on record as praising "Aryan stock" and
| insisting it was right for "a stronger race, a higher-
| grade race" to take the place of indigenous peoples. He
| reportedly did not think "black people were as capable or
| as efficient as white people". In 1911, Churchill banned
| interracial boxing matches so white fighters would not be
| seen losing to black ones. He insisted that Britain and
| the US shared "Anglo-Saxon superiority". He described
| anticolonial campaigners as "savages armed with ideas".
|
| Even his contemporaries found his views on race shocking.
| In the context of Churchill's hard line against providing
| famine relief to Bengal, the colonial secretary, Leo
| Amery, remarked: "On the subject of India, Winston is not
| quite sane ... I didn't see much difference between his
| outlook and Hitler's.""
|
| https://amp.theguardian.com/commentisfree/2021/mar/17/why
| -ca...
|
| >"He referred to Palestinians as "barbaric hordes who ate
| little but camel dung." When quashing insurgents in Sudan
| in the earlier days of his imperial career, Churchill
| boasted of killing three "savages." Contemplating restive
| populations in northwest Asia, he infamously lamented the
| "squeamishness" of his colleagues, who were not in "favor
| of using poisoned gas against uncivilized tribes.""
|
| https://www.washingtonpost.com/news/worldviews/wp/2015/02
| /03...
| elif wrote:
| Also, Alexander Graham Bell supported eugenics because he
| was worried that deaf people procreating created human
| and social divisions.
|
| Any modern medicine gene modification program would
| create the exact human and social divisions he sought to
| avoid... Unless you are somehow able to suddenly do gene
| modification universally throughout the entire planet..
|
| so he doesn't really support your position either.
| elif wrote:
| Helen Keller defended a doctor's 1915 non-intervention in
| the case of a child that was not capable of "the
| possibilities of happiness, intelligence, and power that
| give life its sanctity, and they are absent in the case
| of a poor, misshapen, paralyzed creature", and then later
| supported adoption of disabled children, such as the a
| case of an infant with tumor-induced blindness saying
| "blindness is not the greatest evil, it is only a
| physical handicap. that is life. the annals of progress
| show that much of humanity's finest work has been wrought
| by persons with with a severe handicap, that she may be
| spared to help open the eyes of ignorance"
|
| I hope that she can help you to open your eyes as well.
| rowanG077 wrote:
| I'm not sure what your point is. I'm not advocating for
| killing anyone. I don't think you are arguing in good
| faith here.
| elif wrote:
| you referenced helen keller's non-intervention in an
| instance of infant mortality as evidence that she
| supported eugenics.
|
| It is that erroneous conflation that introduced
| euthanasia for discussion. (also i would say that
| technically intentional non-intervention is not exactly
| killing, so thats not even what i was implying)
|
| I provided evidence that keller, contrarily, saw value in
| genetic defects.
|
| If you have another reason for believing that helen
| keller was a supporter of eugenics, you have failed to
| provide it.
| elif wrote:
| Sorry if i hit a nerve, but obviously if i wasn't
| "arguing in good faith" why would i have so painstakenly
| avoided mentioning hitler for like 10 comments?
|
| conversely, everything i've said has been a direct
| analysis of what you've said.
| elif wrote:
| it has taken us 2 years to give 60% of the planet a $5
| shot despite having 2x world population of shots
| available.
|
| "capability" should not be confused with "universal
| accessibility"
|
| and "some people one hundred years ago did horrible
| things" is a fictional strawman. There are real and
| present reasons why practically eugenics will lead to
| stratified and unjust conditions for humanity in
| practice.
| atlasunshrugged wrote:
| $10M+ now and then in 20 years figure out that changing that
| gene sequence creates a dramatically higher likelihood for
| Alzheimer's or infertility. I personally am not against the
| modification of humans in practice, I think it's an
| interesting opportunity for humans to take control over the
| evolutionary process and optimize ourselves for the world we
| live in now (and future ones), e.g., what if we could
| minimize the amount of sleep needed, or our tolerance to heat
| so climate effects were somewhat mitigated, or so our bodies
| were less affected with long periods in space? The tie-in of
| capitalism to it creates a weird dynamic but I'm not sure I
| see an obvious better solution unless we want to outlaw
| everything except for government approved research and let
| the ideas be at the whims of whatever bureaucrat or political
| appointee happens to be in charge at the time.
| MontyCarloHall wrote:
| >$10M+ now and then in 20 years figure out that changing
| that gene sequence creates a dramatically higher likelihood
| for Alzheimer's or infertility
|
| Not only that, but any genes that are not selected against
| (e.g. your Alzheimer's example, which occurs after
| reproductive age) are now permanently circulating in the
| population, with absolutely zero (humane) way of ever
| removing them.
| dekhn wrote:
| In the short term, a lot of gene therapy focuses on the set
| of diseases where the repair really does seem to be "change
| this one base" and there are no side effects due to
| complex, unknown gene interactions or other unexpected
| phenomena. m And nearly all of it (I haven't looked at the
| details in a while) is just treatment (IE, injections of a
| gene therapy in a post-birth individual), rather than
| preventive by germline manipulation, which IMHO
|
| It's likely that for the time being we'll only use gene
| therapy for things which are recognized as devastating
| diseases and the treatment is extremely reliable; germline
| modification for enhanced attributes in typical individuals
| is still a fairly out-there concept that would probably get
| panned in the media.
| inglor_cz wrote:
| Given that people already travel for IVF to cheaper locations
| abroad (Ukraine was one of them until the war), it is going
| to be more like $100K+ in the future.
|
| Medicine is practised outside the US as well, including high
| tech medicine. And for a much more reasonable price tag.
| daniel-cussen wrote:
| This already is what happens with sexual selection. That is
| the purpose of sexual selection from the point of view of
| genetic integrity. People are designing their babies every
| time they have sex. There's huge amounts of money involved
| there too. And like how do I know the geneticist isn't
| slipping his own in-born DNA in my place, like that fertility
| doctor did or that criminal inseminator who broke into
| poorly-guarded sperm banks and substituted his sperm for that
| of astronauts with Nobel Prizes? Had like 660 kids that way.
|
| Like there good reasons to do this are, OK genetic
| malformation, ie osteogenesis imperfecta, that's a SNIP,
| totally. Or you were raped, want to punish that rapist by
| making the egg have even less genes in common with him than
| it would ordinarily, making his rape counterproductive
| genetically. Another good reason, defensible. Or you want to
| protect rare alleles, considering weaknesses to be strengths,
| this is like a left-handed man marrying a left-handed woman,
| or freckles (I think something about freckles make children
| hate them til they're 19, rare exceptions, not even the
| iconic Lindsay Lohan accepted her own freckles). Preserving
| their identity and diversity. Don't pass laws as much as
| using judgment to decide, individually and collectively, what
| the future will be. Talk and think instead of setting up
| magic words for lawyers to copy-paste--an isomorphic problem
| to genetic design.
|
| No fucking blind copy-paste, don't use copy-paste with your
| copy paste to copy-paste yourself.
| Gatsky wrote:
| Some problems come to mind:
|
| - this is performing an irreversible procedure on a person
| without their consent. Justifiable for a disease but less so
| for vanity traits.
|
| - genes are pleiotropic and modifying multiple genes could
| have unexpected effects. An easy example is that taller
| people have a higher risk of cancer. Barring some great
| advance in predicting the effects of genetic changes, this
| will remain a problem.
|
| - it has a homogenising effect, optimising for traits a
| culture finds appealing and that can be easily measured. You
| will eventually get a eugenic army that all look like
| swimwear models and score highly on IQ tests.
|
| At the same time, I think that modifying the organism is the
| only way to get rid of diseases like heart disease and
| cancer.
| ineptech wrote:
| This doesn't really pass the sniff test; if there were any
| easy one-gene changes that resulted in unambiguously better
| results, it's highly likely that we'd all have them already.
| pilom wrote:
| BCRA mutations: "It's estimated that 55 - 65% of women with
| the BRCA1 mutation will develop breast cancer before age
| 70" [0] ApoE4: "individuals with two versions of the ApoE 4
| gene have a 50% chance of developing Alzheimer's" [1] HTT:
| The Huntingtons gene. If you have the wrong version of this
| gene, you will get Huntington' disease.
|
| All that to say that, in these cases, sure _most_ people
| have positive traits from these genes, not all do and we
| could theoretically use CRISPR to change people with the
| negative versions of these genes to the positive versions
| of these genes.
|
| [0]: https://www.nationalbreastcancer.org/what-is-brca
| [1]:https://www.alzheimersorganization.org/alzheimers-gene-
| apoe4
| elevaet wrote:
| Well, these aren't unambiguously "better results", not in a
| biological sense. Just better in terms of what our culture
| values, and not necessarily better survival and
| reproduction.
| dharma1 wrote:
| memes manipulating genes
| rootsudo wrote:
| This is cool, so in laymans terms - you can disable the bad
| "genes" and just express/enable/push the "good ones."
|
| So how do we define what is a bad gene? If we use crispr, can we
| turn it off on an actual, live, aging human being or only before
| they're "born" or such?
|
| Is there a good resource/book that gets someone from zero to a
| basic biological understanding and background of this and above?
| I _really_ have no idea, nor do I know who to ask. :(
| cvccvroomvroom wrote:
| Not in the field.
|
| Q: How can the human genome be "mapped" without sampling and
| sequencing genetic material from millions of individuals? Is it a
| sequencing of one individual?
| eibhinn wrote:
| We have thousands of human genomes sequenced now.
| mdaniel wrote:
| > New CRISPR-based map(ping process) ties every human gene to its
| function
|
| Maybe it's because I'm not in that industry, but I was looking
| for a graphical gizmo that I could click on a gene and see
| functions but they mean "map" in its functional programming term
|
| Although clicking through the first link does say "Interactive
| Website under construction..." so maybe this was just submitted
| too early or something
| popcube wrote:
| you can just try ensembl or ucsc genome browser
| jhgb wrote:
| > but they mean "map" in its functional programming term
|
| We just called it "mathematical term" back in the day. :)
| aaronblohowiak wrote:
| Paging doctor Church, paging doctor Church, your patient
| Turing is here to see you
| dekhn wrote:
| Here's a link to the gene they mention: C7orf26
| https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtMod...
|
| To understand its function, it has its own wikipedia page(!)
| https://en.wikipedia.org/wiki/C7orf26 It's one of the remaining
| proteins whose "function" (to the extent that proteins can be
| said to have a "function") has not been reliably determined.
|
| There are sites for protein function, my favorite is Uniprot:
| https://www.uniprot.org/uniprot/Q96N11
|
| as you can see, they don't really know what it does: "Probable
| component of the Integrator (INT) complex, a complex involved
| in the small nuclear RNAs (snRNA) U1 and U2 transcription and
| in their 3'-box-dependent processing.".
|
| The integrator complex is an important bit of machinery that
| helps transcript DNA to RNA on its path to protein expression:
| https://www.embl.org/news/science/at-the-core-of-the-integra...
|
| In general, data presentation in biology is a pretty mixed bag.
| The field never attracted the level of UX investment that you
| see at ad-driven companies.
| lysozyme wrote:
| That's true, software for biology tends to be terribly,
| almost comically bad, with one-off file formats, brittle data
| interchange, and impossible-to-maintain code being the norm.
| With user interface and ergonomics being the most neglected
| aspect. Why do you think that is?
|
| Surely there is plenty of money in biology these days to hire
| a good designers to design good user experiences. Surely
| better user experience for biology software would lead to
| better understanding of biological systems and better
| outcomes in bioengineering.
|
| Where are the polished, powerful design tools for biology
| like those that exist for other fields like online
| advertising that routinely process and distill huge amounts
| of lightly-structured data?
| Psyladine wrote:
| I've been trying to break into biotech for years...short
| answer is they want biologists, not programmers, and don't
| appreciate skillsets that aren't already secondary to PHD
| industry-relevant experience.
| asah wrote:
| Oh, so like Wall Street in the 80-90s, gotcha.
| danieltillett wrote:
| The reason why is it is easier to train a biologist to
| become a programmer than it is to train a programmer to
| become a biologist. Sure the quality of biologist-turned-
| programmer code will often not be great, but it will
| usually answer the question asked.
| timy2shoes wrote:
| Not in my experience. The reason is because of funding.
| NIH grants are focused on biological discoveries and not
| so much around infrastructure. So you can get funding to
| build a tool, but not so much to maintain it. The
| downstream effect is that tools and websites are stuck in
| the era in which they were created, databases are not
| updated, and tools are broken because the grad student
| left and now there's no one to respond to issues.
| doublepg23 wrote:
| The argument I've heard for such domain specific software
| having poor UIs is refined UIs only matter for a the first
| third "10,000 hours". After becoming an expert you simply
| become used to the software. Anybody professionally using
| the software would only see a _loss_ in productivity - even
| if the UI changes for the better.
|
| See also Emacs, maybe?
| eweitz wrote:
| User interfaces for biology have drastically improved over
| the last 10 years.
|
| Domain-specific tools like genome browsers, protein
| viewers, or phylogenetic explorers [1-3] almost all look
| and feel a lot better than they did in 2012.
|
| The biggest exception here is UCSC Genome Browser, which
| has an old-school design and web technology stack. That
| said, it's steadily added features over the years, has
| substantially sleekened UX in its periphery, and remains
| widely used.
|
| There are also bespoke visual design resources for biology
| applications that are good and getting better, like
| BioRender and PhyloPic [4-5]. There are multi-tiered
| packages like Dash Bio that wrap biology components
| together [6]. There's a Blender biology community, too!
|
| ---
|
| 1. Genome browsers and components:
| https://jbrowse.org/jb2/,
| https://www.ncbi.nlm.nih.gov/genome/gdv,
| https://igv.org/app, https://eweitz.github.io/ideogram
|
| 2. Protein viewers: https://pymol.org/,
| https://nglviewer.org/ngl/
|
| 3. Phylogenetic explorers: https://clades.nextstrain.org/
|
| 4. https://biorender.com/
|
| 5. http://phylopic.org/
|
| 6. https://github.com/plotly/dash-bio,
| https://dash.gallery/Portal/?search=[Pharma]
| jltsiren wrote:
| Software quality improves once you move to older well-
| established problems, where developers who are not actively
| involved in research can contribute.
|
| If you work with cutting-edge problems, the job of a
| programmer is turning vaguely expressed biological
| questions into software. The first attempts will inevitably
| fail, as they try to solve the wrong problem in the wrong
| way. Technical debt will accumulate at an incredible pace,
| as your understanding of the problem improves and the
| software becomes something very different from what you
| originally imagined.
| hyperpallium2 wrote:
| ...but it's not a function function, because one gene can have
| many functions.
| bumby wrote:
| For those interested in further reading:
|
| https://en.m.wikipedia.org/wiki/Pleiotropy
| caycep wrote:
| it seems like that is a whole other skillset vs. biology
| graduate students...I know the Allen Institute employs data vis
| people to write visualisation tools like this in d3/react or
| whatever the web api du jour is, but they are separate from the
| science folks
| grej wrote:
| Another cool thing, their paper mentions that, "The specific
| implementation is based on the python package torch-two-sample,
| modified to use numba for improved performance." (
| https://www.cell.com/action/showPdf?pii=S0092-8674%2822%2900... )
|
| If you haven't checked out the numba package, definitely worth a
| look for custom numerical computing in Python!
|
| disclosure - have made a small contribution to the package.
| atlasunshrugged wrote:
| Anyone know where the state of the art is happening in applied
| 'designer baby' tech? I feel like there hasn't been much news
| since the arrest of the scientist who claimed to be the first to
| change the genes of live kids but I'm shocked there aren't some
| people out there pushing the envelope on this (and/or
| commercializing it).
| cauthon wrote:
| Never underestimate MIT's ability to oversell itself.
|
| (EDIT: see below, this is directed at the press release, which I
| perceive to be overstating the achievements presented in the
| paper, not the quality of the paper itself)
| warent wrote:
| Care to elaborate? This just seems like an empty criticism
| without any value or substance
| cauthon wrote:
| Sure. A genome-wide perturb-seq experiment is a huge (and
| expensive) technical accomplishment, but the authors did not
| "map every human gene to its function". (Nor did they claim
| to, it's press release hyperbole.)
|
| One, there's ~20k protein-coding genes in the human genome,
| and they screened ~10k, analyzing about 2k (fig 2a).
|
| Two, all the functional annotation is based off transcription
| profiles. They essentially looked for clusters of genes with
| correlated expression, and assigned function based on genes
| with previous annotations (fig 2d, S4).
|
| It's a good resource, but there's a lot more molecular work
| to be done to validate the function of these genes.
| timy2shoes wrote:
| > Two, all the functional annotation is based off
| transcription profiles. They essentially looked for
| clusters of genes with correlated expression, and assigned
| function based on genes with previous annotations
|
| This is an important point, because if you've ever worked
| with single cell data you'll know that the transcriptional
| profile is extremely noisy and your transcriptional profile
| to cell type map has many researcher degrees of freedom. I
| heard a story about a paper early in the single cell work
| that started with 53 cell types and after review ended up
| with 37 cell types. Are those true cell types? Did the
| experimenters validate that those cell types all performed
| different functions? Well, of course not. That's way too
| much work.
|
| Then add on technological biases, which make mapping
| between technologies difficult. I say this because they
| used a new sequencing technology that appears to have
| homopolymer bias
| (https://twitter.com/lpachter/status/1533875723995185153),
| which will bias the gene quantification.
| cauthon wrote:
| > I say this because they used a new sequencing
| technology that appears to have homopolymer bias (https:/
| /twitter.com/lpachter/status/1533875723995185153), which
| will bias the gene quantification.
|
| I believe they used Illumina for the results presented in
| the main text and then re-sequenced with Ultima and
| replicated a subset of the analyses (fig s13). The Ultima
| proof-of-concept didn't appear to be relevant to the main
| study/conclusions
| dekhn wrote:
| Is there a way to get the parent comment unflagged? The
| response from the commenter shows they have a lot to
| contribute, technically speaking.
| cauthon wrote:
| Thanks. I'll admit the first comment didn't contribute much
| and apologize for not including my thoughts from the
| follow-up. I just don't care for these sorts of hyperbolic
| press releases.
|
| It's part of the game, the big players are as good at sales
| as they are at science, but I've never been a fan of it.
| dekhn wrote:
| Useful book that any starting professor should
| understand, even if they don't want to admit they are
| playing a game. science-by-press-release is a technique
| to master if you want to both maximize the impact of your
| work, and get tenure.
|
| https://www.amazon.com/Winning-Games-Scientists-Play-
| Sinderm...
| Noumenon72 wrote:
| I have `showdead` turned on in my profile, and I saw this
| whole comment chain. Will people with it turned off still
| see the replies?
| wolverine876 wrote:
| You can click 'vouch'.
| dekhn wrote:
| Thanks, I didn't realize you had to click through to the
| comment to see that.
| coryfklein wrote:
| Wait do we even know that every human gene has a 1:1 mapping to a
| function in the body? I think the code analogy to this would be
| trying to map "C++ if statements" to a particular feature in your
| product. I'd expect something as complicated as the genome would
| have a much richer and complicated interaction with biological
| feature expression.
|
| I'm probably simply misunderstanding; maybe Weissman's data is a
| 1:N mapping?
| shpongled wrote:
| We already know that many genes have more than one function
| (especially when you consider that one gene can produce many
| protein products)
| elif wrote:
| I think mpeg encoding would be a better demonstrative than
| code...
|
| Where data is lost, details are lost, but the end result still
| typically renders into something recognizable. If you lose an
| iframe, you end up with a more serious deformity. Whereas code
| either does exactly what it says or does nothing at all, and
| knocking out a single statement is almost certain to break
| everything.
| astrange wrote:
| This kind of shallow presentation is common for genetics;
| compare reporting genetic traits by SNPs and implying the SNPs
| "cause" them, which is like diffing two versions of a program
| and saying X new feature happens because there's a letter 'n'
| in one program and not the other.
| axg11 wrote:
| There's not any type of mapping and this is what makes biology
| so difficult to study and understand. One gene can affect
| anywhere from zero other genes to every single gene. We also
| need to account for effects at every level of the central dogma
| of biology. Knockout of a gene can affect genetics, RNA,
| protein, and much more we don't even know about yet. The other
| underestimated complicating factor is that biology is very
| nonlinear. A 10% increase in gene expression could lead to no
| resulting effect, whereas an 11% increase in expression could
| upregulate downstream genes by 1000x.
| hgomersall wrote:
| I remember going to a really interesting talk in which the
| proposal was to represent the transcriptome as a
| probabilistic generative model. That felt like getting
| something close to an appreciation of the complexity.
| Balgair wrote:
| > Wait do we even know that every human gene has a 1:1 mapping
| to a function in the body?
|
| When it comes to biology, the answer is typically: It's
| complicated. I'll give two examples, melanin and the gene for
| vitamin-C.
|
| The process to make melanin is a bit complex, but suffice to
| say the chemical is produced. From there, it is used in at
| least two way you are probably familiar with: sleep and
| tanning. Our bodies uses melanin production to help regulate
| our sleep cycle. Also, through the quirks of evolution, we use
| it to help stop UV radiation and keep our skin safe. At the end
| of the day, a complex process that includes a few genes maps to
| multiple functions.
|
| The gene for vitamin-C production is another example. In
| humans, some primates, and guinea pigs, this one gene is
| mutated. As such, we can't produce vitamin-C internally and we
| have to get it from our diet. This single gene _had_ a function
| in our ancestors, but no longer does. I think you can argue
| that it 's lack of function is a psuedo-function for our
| ancestors to eat more fruits, but I don't really buy that.
| Evolutionary, we would be better off with the non-mutated gene
| than with what we got now (ask any scurvy survivor or Inuit).
|
| Generally, I'd say that most of the genes in our code are more
| like the mutated vitamin-C gene than the melanin ones. They had
| specific functions sometime in our history, but no longer do.
| Kinda like a vestigial organ or the eyes of a cave fish.
| willlma wrote:
| Melanin affects sleep? Sure you're not confusing it with
| melatonin?
| johnsimer wrote:
| Parent might indeed mean melanin,
| https://pubmed.ncbi.nlm.nih.gov/23477948/
| geysersam wrote:
| I'm not a biologist. Still, do genes really have "functions"?
| Guess some have, such as producing an enzyme to break down a
| particular kind of suger. But that this would be the case for
| _every human gene_ sounds unlikely to me.
| projektfu wrote:
| A gene is a DNA (or RNA) sequence that codes for some protein
| or RNA product. There are other functional sequences in DNA but
| they're not called genes.
|
| https://en.wikipedia.org/wiki/Gene?wprov=sfti1
| dekhn wrote:
| For your last sentence: that's right, to get any press
| attention today you have to basically say you've solved all
| cancer or done something pan-genomic, in a way that massively
| overstates the importance of the specific result and its impact
| on health care delivery.
|
| That said, Jonathan Weissman is a great guy who has pushed the
| field forward and the techniques they are using really are
| powerful.
| panabee wrote:
| thanks for all your comments and insights. can you recommend
| other people to follow on the leading edge of integrating
| technology and biology?
| commandlinefan wrote:
| > do genes really have "functions"?
|
| Makes me think of Douglas Hofstatder's "grandma neuron":
| https://www.livescience.com/grandmother-neurons-discovery.ht...
| radicality wrote:
| His explanation in GEB of how genes, DNA, and RNA function
| was probably the clearest one I've ever read. It's been a
| while and I forgot the details, but reading his analogies
| made everything click at the time. Maybe it's time to re-read
| GEB.
| david_l_lin wrote:
| All genes have a function. This paper helps us understand genes
| of unknown function (which is a LOT of them).
|
| Some of these functions are not intuitive: maybe they regulate
| the function of another protein, maybe they only function in
| the context of a particular stressor, etc. You can think of
| nearly unlimited scenarios to apply and you start to understand
| the complexity of understanding how a gene functions.
| dekhn wrote:
| "All genes have a function" <- this is a generalist statement
| that is wrong in its specifics, but also raises semantic
| question of what "function" actually means.
| david_l_lin wrote:
| A lot of studies have shown that literally taking up
| genomic space is a function. So by definition, all genes
| have a function. Non-genes have functions. The topological
| organization of genomes is a function.
| pfisherman wrote:
| "All genes have a function" is analogous to saying, "All
| particles play a role in our physical reality". This should
| be uncontroversial.
| dekhn wrote:
| This is a bit of a semantic argument, but gene function
| is a fairly nebulous term. The essence of what I am
| saying is that there may be proteins that currently have
| no actual function, aren't under functional selection,
| yet are duplicated, transcribed, and expressed (not just
| pseudogenes).
|
| Function is a rabbit hole. Biologists get in big
| arguments about the semantics of this all the time
| (http://cryptogenomicon.org/encode-says-what.html). I
| don't really care. I care about the minimal set of
| necessary proteins for a model organism to exist and
| reproduce in a media-rich environment. And, whether there
| are actually subsets of mutually compensatory groups of
| proteins instead of a single minimal set.
|
| Protein function is one of those things that, at first,
| seems really simple to define, but the further you go
| down the rabbit hole, the more complicated it gets, until
| it's fractally complex and you realize that not only does
| the exception prove the rule, it's all exceptions.
|
| See also:
| https://en.wikipedia.org/wiki/Enzyme_promiscuity
| pfisherman wrote:
| I think the semantics are largely dependent on the level
| of abstraction you are reasoning at. Here I use
| abstraction loosely to refer to conceptual or physical
| scale / granularity / resolution. For example, we are
| (probably) both using the term "gene" as shorthand for
| the concept of "gene or gene product(s)". Likewise the
| term function can refer to phenomena occurring on
| molecular, cellular, etc length scales, or more amorphous
| groupings of phenomena such as "flux" through a
| biological pathway.
|
| But if you really drill down into the nitty gritty, then
| the "function" of a "gene" is its complete set of state
| altering / modifying relationships with other bio
| entities. In this sense, all bio entities have functions
| because they all have functional relationships with other
| bio entities.
|
| So yes, all genes, pseudo genes, isoforms, etc have a
| "function" even if it is redundant, taking up space, or
| just soaking up some of the pool of tRNA.
|
| Also the minimal genome stuff is pretty fascinating! One
| of the best research questions I've ever heard was, "what
| are the essential genes of unknown function doing?"
| dekhn wrote:
| The problem is that proteins do some things passively
| unrelated to (say) their enzymatic ability. Is that
| secondary functionality a function? What if it's binding
| a molecule, but then releasing it before the catalysis
| occurs (wasted effort).
|
| I mean, I know a person in grad school who worked on
| finding the function of a protein for a long time. It was
| given by a collaborator and had high sequence similarity
| to a known enzyme in a related species. She tried every
| possible functionality test to see if it was a protease,
| or any of a hundred other enzymatic reactions. Eventually
| it turned out the collaborator had mistakenly given them
| an alanine-scanned protein with the necessary functional
| residues replaced, so she never detected any activity
| because there wasn't any. Does that mean the protein had
| no "function"? It was binding water molecules, even
| plausible substrate, but just never helping a transition
| state form. Even if you replaced the working version of
| the protein with the broken version in an organism, if it
| wasn't a completely necessary protein, it would continue
| to reside in the genome with no function for some time
| until (perhaps) neutral mutation due to lack of
| functional selection caused the protein to be non-
| expressed and it starts to rot away into a pseudogene.
|
| The main problem with your research question is that it
| still hasn't been completely resolved- there are proteins
| remaining which are necessary, but their functions are
| unknown.
| axg11 wrote:
| > All genes have a function.
|
| For the benefit of readers unfamiliar with the field: this is
| wrong.
|
| You can show this experimentally. Construct a gene that
| produces a non-human protein and introduce this to a human
| cell/genome. That gene would not have a "function" but still
| exists in the genome. This is actually happening all the
| time. Some viruses integrate their genomes when infecting
| cells. Viral integration is one of the factors that shapes
| genome evolution.
| david_l_lin wrote:
| Even an exogenously expressed non-human protein still has a
| "function". even if you force it to be expressed. We may
| not understand its effects, but it is certainly doing
| something. Even just taking up a space is a biological
| function, which an exogenously expressed protein is doing.
| The same applies to genes that do not get translated to
| protein, by definition of "doing something" they have a
| function.
|
| Your viral integration example is actually a perfect
| example of one where all genes indeed do a have a function,
| but they are not readily apparent to us. Genes that control
| latency may not expressed until specific conditions, and
| that is their function, to control expression. Some genes
| control integration.
|
| I spent 5 years of my life doing my PhD studying viral
| replication, and the "unknown function of viral genes" was
| a constant topic of discussion, but we all agreed, they
| have a function.
| dekhn wrote:
| You're conflating "consequences and effects" with
| "function". The former is things that happen due to the
| physics, the latter is about intent or utility.
|
| "Taking up space in the genome is a function" is a great
| example of this. While I'm sure you can find examples of
| "spacers that when deleted are fatal", the fitness effect
| of protein-coding regions that contain no utility is
| still an area of research. To me, functionality requires
| selection, although that's probably not necessary or
| sufficient!
| eurasiantiger wrote:
| All human proteins are encoded in genes.
|
| https://en.wikipedia.org/wiki/Category:Human_proteins
| [deleted]
| Obi_Juan_Kenobi wrote:
| A gene is essentially defined as having a gene product, either
| an RNA or protein. So yes, all genes are functional.
|
| Genes that aren't translated into protein sequences (noncoding
| genes) can create structural RNAs as with Ribosomes, microRNAs
| that have regulatory functions, etc.
|
| There are lots of non-gene genetic elements that do things,
| though. Many are involved in gene regulation, affecting the
| transcription rates of nearby loci through a variety of
| mechanisms. There are also vast swaths of inactivated
| transposons, retroviruses, and other repetitive genetic
| sequence.
| imchillyb wrote:
| This is akin to taking an automobile apart piece-by-piece, not to
| determine its function but just to figure out if the automobile
| fails substantially by removing say a taillight, dome light, dash
| light, or wiper delay fuse.
|
| The car's not gonna fail for each piece, it'll take forever to
| determine what pieces are absolutely necessary, and it doesn't
| tell ya shit about what the pieces functions are.
|
| Neat, but ultimately inefficient and exceedingly limited in
| necessary detail to make the claim in the article's title.
| [deleted]
| throwawayarnty wrote:
| One model of how science progresses is a few pioneers breaking
| new ground and then everyone else rushing in to pick up low
| hanging fruit in the new field.
|
| Looks like Weissman lab has consistently been breaking new ground
| over and over again. Extremely impressive and very few labs in
| the world have such a track record.
| jzer0cool wrote:
| Would love to dive in looking into the data, but I don't
| understand it. Could someone share how to "read" the data file
| both from non-technical and technical perspective. Right now not
| sure how to interpret the data and I also do not have a
| biology/gene background.
| balsam wrote:
| Do you have a direct link to the data you mention? Something
| more specific than a general "help! I am lost!" would go a long
| way. I dont really see it in the article.
|
| OTOH, here is the wikipage of the one gene mentioned
| https://en.wikipedia.org/wiki/C7orf26
|
| EDIT: dekhn below expands on this
| bryans wrote:
| An article from MIT:TR in the early 2000s always stuck with me as
| an example of how intricate and interconnected genes really are.
| Researchers using fruit flies found one born with white eyes, and
| they narrowed the mutation to a specific gene. They were able to
| modify it in vivo to reliably produce white eyes, but the change
| had an unexpected second outcome, which was that white-eyed males
| would only attempt to mate with other males.
|
| Years later, there was a group who cited that fruit fly paper
| when they proposed the same methodology to control mosquito
| populations, but I'm not sure if they ever recreated the male
| preference. The mosquito gene editing did pan out, but the method
| is different in that it doesn't allow females to survive, while
| males will go on to mate with other non-edited populations and
| spread the female-killing gene.
| jmyeet wrote:
| This is really amazing.
|
| Of course I was aware of the Human Genome Project and mapping DNA
| in general. I was also aware that figuring out all the proteins
| in a cell and what they do is a whole other problem.
|
| I didn't realize they'd made this much progress. It's not
| complete obviously but being able to figure out gene expression
| is a _massive_ step forward. The ability to switch off genes
| (this is where the CRISPR editing comes in) and seeing what
| changes is just astounding (there was an example of chromosome
| segregation).
|
| It's known that certain proteins mediate certain processes where
| the presence of that protein or the absence of it can lead to a
| condition or disease. The potential impact here for treating
| genetic disorders I think cannot be overstated.
|
| Between this an the technology behind mRNA vaccines, I really
| wonder if the 21st century will lead to the effective elimination
| of many diseases.
| tandr wrote:
| > Between this an the technology behind mRNA vaccines, I really
| wonder if the 21st century will lead to the effective
| elimination of many diseases.
|
| And, due to errors and human mistakes, possible creation of
| some new, or old-but-improved ones...
| jjtheblunt wrote:
| > The ability to switch off genes (this is where the CRISPR
| editing comes in)
|
| i think your wording is ambiguous : CRISPR can edit the
| sequence, but "switch off" has an association with methylation
| of items in the sequence, orthogonal to the sequence itself.
| Obi_Juan_Kenobi wrote:
| You misunderstand.
|
| We've being doing genetics for decades. Molecular biology
| without mutant studies wouldn't exist. It's the foundation of
| the field.
|
| All this is is a difference in scale. But it is a very crude
| tool; really understanding gene function involves studying it
| in relevant contexts. Looking at cells in tissue culture can
| give you some ideas or hints about how it functions, but the
| critical insight might require certain cell types or gene
| regulatory environments.
|
| What data like these do is inform hypothesis generation and
| refine the interpretation of genomic data. It is important
| work, but does not replace doing actual biology.
|
| What you're talking about is essentially saying we just
| invented molecular biology. Which is obviously not the case.
| Filligree wrote:
| > I didn't realize they'd made this much progress. It's not
| complete obviously but being able to figure out gene expression
| is a massive step forward. The ability to switch off genes
| (this is where the CRISPR editing comes in) and seeing what
| changes is just astounding (there was an example of chromosome
| segregation).
|
| The protein folding problem was solved earlier this year. You
| can expect a lot more coming in this vein... interesting times.
| dekhn wrote:
| the protein structure prediction problem was solved, not
| protein folding. Different field. Also, it wasn't really much
| "solved", so much as prediction got as good as the metric
| used to compare the predictions to reality, so we can't
| really say for sure whether the predictions are better than
| golden labels or not.
| hirako2000 wrote:
| The 21st centry may lead to the definitive elimination of
| humans, of desease i can only imagine their numbers going up,
| not down.
|
| "that's where CRISPR editing comes in". To edit the DNA of
| congeniality diseased people? I doubt the business will focus
| primarily on this category of patients, unfortunately. but I
| still hope the worst will be avoided when/if using this tech
| kind of tech.
| BurningFrog wrote:
| I suspect FDA regulations will have to be redesigned a lot to
| make most DNA editing treatments economically possible.
| hirako2000 wrote:
| If they approved the sort of recent treatment they
| approved, for that scale of deployment (billions of
| individuals within a year) it wouldn't surprise me they
| will approve anything, given enough lobbying. No worry to
| have with FDA becoming an obstacle.
| moron4hire wrote:
| So, like... I'm pretty ignorant on biology, genetics, gene
| editing, and such. But... could one alter their genetics for,
| say, poor eyesight and eventually have better eyes? I mean, I
| imagine that there is a shelf life for cells already in the body
| and they don't just go away right away. But they are also
| constantly being replaced, right? So... can I just... rewrite my
| genome to replace my eye cells with "better" eye cells?
|
| And--hypothetically speaking, for sure, certainly, I assure you--
| who might be capable of such a thing, and what might they like as
| remuneration?
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