[HN Gopher] Gain of Function? Not So Fast
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Gain of Function? Not So Fast
Author : _Microft
Score : 53 points
Date : 2022-10-18 18:16 UTC (4 hours ago)
(HTM) web link (www.science.org)
(TXT) w3m dump (www.science.org)
| epivosism wrote:
| Author has a reasonably open mind on virus origins, article from
| may 2021 https://www.science.org/content/blog-post/coronavirus-
| origin...
|
| He's not circling the wagons defending natural origins in the
| above.
| chubs wrote:
| If there's anything I've learned growing up in various
| churches... the people who aren't open-minded, aren't worth
| listening to. Thanks for highlighting that this author seems be
| worth listening to.
| xupybd wrote:
| >But before jumping out of your chair, consider that when these
| mice were exposed to the original Wuhan coronavirus that 100% of
| them died.
|
| Well that is very different to the first news I saw about this.
| Tim Pool reported that in the first test no mice died. I guess I
| have to be more careful about what I listen to.
| [deleted]
| PathOfEclipse wrote:
| So, wait. It's not gain-of-function research unless they
| successfully make a more dangerous virus? These "scientists" are
| getting so much better at politics. Playing with the definitions
| of words is a class political tactic!
|
| I'm going to quote one of the scientists the article actually
| quoted themselves:
|
| "Now, the outcome of the experiment was not clear. You could have
| assumed that the virus, compared to the ancestral virus is less
| pathogenic (which was the case). But it could also have been more
| pathogenic. Therefore, these experiments need to be done in
| appropriate biosafety laboratories. And, if the virus can become
| more pathogenic and falls into certain categories, you also need
| permission from the US government to perform the experiment -
| especially if they fund your research. And that is what was not
| done here."
|
| Later on, on the same subject, he literally says: "Having said
| all that, I absolutely think GOF research should be tightly
| regulated and controlled."
|
| Our scientific institutions surely have become wholly corrupted
| by politics. This is gain-of-function research. Whether you think
| that type of research should be conducted or not is moot. The
| scientist quoted said he thinks this was not dangerous GOF
| research, but still needed to be tightly regulated.
| chomp wrote:
| > It's not gain-of-function research unless they successfully
| make a more dangerous virus?
|
| Yes, that's more or less the definition of the term.
|
| > Playing with the definitions of words is a class political
| tactic!
|
| I definitely get the feeling that there are people that like to
| twist words to suit their goals.
|
| > This is gain-of-function research.
|
| From where are you sourcing your definition of the term?
|
| This doesn't appear to be gain of function research (from the
| strict definition of the term) but in this day and age when the
| virus is ground-zero for politics, it's probably not
| politically wise to do research on it along these lines. To
| this end, where what's politically favorable influences the
| science we do, I do agree that politics is inevitably
| corrupting good research.
| tsimionescu wrote:
| > Yes, that's more or less the definition of the term.
|
| You can't characterize a type of research by its results for
| purposes of evaluating its methods. If we want to say "GOF
| research should only be carried out in a lab that meets such
| and such criteria", or "we shouldn't fund GOF research at
| all", then the definition must be related to what the
| research _may_ do, since we need to evaluate it before we
| know it 's result.
| peteradio wrote:
| > Gain-of-function research is medical research that
| genetically alters an organism in a way that may enhance the
| biological functions of gene products.
|
| It is not constrained to virulence.
| radus wrote:
| The research described in the pre-print aimed to understand the
| mechanism of action behind the decrease in pathogenicity
| observed with Omicron strains, and specifically, whether
| mutations in the Omicron spike protein can account for that
| decrease. The experiment they carried out is about the most
| straightforward one you could draw up to begin to answer that
| question, and I would never even think to characterize it as a
| "gain of function" experiment. If you want to classify this
| study as GOF then you might as well do the same with any study
| of a virus where even a point mutation is made - good luck
| doing any virology under those conditions.
| StanislavPetrov wrote:
| >The research described in the pre-print aimed to understand
|
| The "aim" or the intention is entirely irrelevant.
|
| >If you want to classify this study as GOF then you might as
| well do the same with any study of a virus where even a point
| mutation is made - good luck doing any virology under those
| conditions.
|
| Good, let's stop mutating viruses in labs. Better to have no
| virology at all than to let these madmen continue to gamble
| with all of our lives.
| salawat wrote:
| Changing genome is literally changing source code.
|
| You just copied a new function moreEffectiveImmuneDodge()
| into a viral substrate that was previously
| lessEffectiveImmuneDodge()
|
| This act of composition apparently created
| willStillTryToKillYou().withAMoreEffectiveImmuneDodge()
|
| Look, I get it, you've gotta run a trial.
|
| _Do it in BSL4_. Not BSL3. You are mixing snippets from two
| known, highly transmissable, highly pathogenic set of
| substrates. You should not be going into utilizing either of
| these ingredients as a chimera under the misguidedly
| optimistic thought _you won 't make something worse_. The
| least you could do is demonstrate an elevated level of
| caution of your treatment of it until your experimental
| results prove the end result isn't as bad or worse than the
| originals.
|
| How is that so hard an assumption to work under? If we're
| locking GoF behind "I succesfully created a more dangerous
| pathogen" rather than "I'm adding a feature to a virus that
| wasn't there", then GoF is a useless term.
| cykros wrote:
| They would have loved to, but BU's proposed BSL4 lab got
| blocked back in the early 2000's because, well, they wanted
| to put it in the heart of Roxbury. And considering that
| they've had at least one or two leaks from their existing
| BSL3 facilities in Boston, that struck folks nearby
| as...well, not the best place to put a BSL4 (especially a
| handful of years after the Anthrax releases traced as
| originating from Ft. Dietrich in the wake of 9/11).
|
| There are things that you COULD do with scientific
| procedure that would absolutely have some beneficial
| results where the potential human cost is simply too high
| to ethically justify (for example, see: a ton of science
| performed under the Third Reich). Perhaps some day we can
| do some of this work in a safe manner off-planet (ideally,
| without even needing humans on board the platforms where
| the virii are being manipulated). We're not there yet, and
| ethicists need to be willing to step in to keep things in
| check.
| tsimionescu wrote:
| > They would have loved to, but BU's proposed BSL4 lab
| got blocked back in the early 2000's because, well, they
| wanted to put it in the heart of Roxbury.
|
| By this logic, if they didn't gave a BSL3 lab they should
| have still done it in a BSL2 lab, and by the same logic,
| utlimately in their garage.
|
| If you don't have access to the proper facilities, _don
| 't do the research_. Anything else should be a career-
| ending move.
| dstein5 wrote:
| Science reporting has been dead for decades, these rags are
| glorified blogs that race bait and endorse politicians.
| [deleted]
| tptacek wrote:
| It reads as if you just scare-quoted "scientist" in referring
| to Derek Lowe. Was that your intention?
| throwawaymaths wrote:
| I'm a former PhD scientist who has done (non-pathogenic) GOF
| research -- we were trying to make energy production more
| efficient -- and I support the comment of GP.
| tptacek wrote:
| First, I'm genuinely just asking if I understand the
| comment well enough. Did you read it the same way I did?
|
| Second, would you classify Derek Lowe as a scientist, or a
| "scientist"? (If you think there's no difference, then
| you're reading the parent comment differently from me,
| which is useful information.)
| camdenlock wrote:
| Is "scientist" some sort of sacred occupation? Are you a
| scientist? Can anyone be a scientist? Are credentials
| required? Which credentials do you accept? Is Derek Lowe
| sufficiently credentialed such that his statements should
| be treated as sacred?
| tptacek wrote:
| No. Not really. Yes. Maybe. A PhD is a good start. No.
|
| I don't think you understand what I'm asking.
| PathOfEclipse wrote:
| if the scare-quotes bother you, ignore them, since they
| weren't the main point of the comment, but the quotes
| were meant to convey that many scientists today often
| don't behave scientifically, but instead behave like
| politicians, activists, or moralizers, even if they have
| the credentials of a scientist and do scientific things
| for a living. There are so many things said by scientists
| and scientific authorities today that are at best purely
| the opinion of the person speaking, or have very weak
| observational evidence supporting them, but these things
| are often given the veneer of science anyways.
| [deleted]
| tptacek wrote:
| You wrote it, so I'm not ignoring it; I'm taking what you
| said seriously. Can you articulate the way in which Derek
| Lowe is "not behaving scientifically"?
| PathOfEclipse wrote:
| If you're going to take what I say seriously, then I
| think you should focus first on the main point of the
| comment, and not a minor detail, but whatever. I can play
| ball.
|
| Assuming Derek Lowe the author of the article, I feel
| like my first comment covered your question He's playing
| with the definition of a politically-charged word,
| claiming that a GOF experiment isn't so unless it
| successfully creates a more virulent virus. I get that
| the definition of words isn't set in stone and there can
| be ambiguity involved, but this seems like a very
| dishonest take on what GOF research actually is.
|
| He even quoted a scientist whose conclusion is the exact
| opposite of his, that this is in fact GOF research, and
| failed to mention the fact!
|
| To add to my original comment, he used the phrase "real
| virologist" at least three times. This is charged
| language that implies a lot of people in these
| conversations don't know what they are talking about.
| This is not the behavior I expect out of scientists.
| Well, that's not true anymore. Nowadays, this is
| unfortunately the kind of behavior I do expect out of
| scientists that write articles for sites like
| science.org.
| bena wrote:
| And tptacek felt that your use of quotes around
| "scientists" was also charged to imply Lowe wasn't
| entirely credible. But he wanted to make sure that's that
| what you were claiming because Lowe apparently has the
| academic credentials to lay claim to the appellation.
|
| You also want to accuse him of not engaging with your
| main point. But from your posts, I would say your main
| point is that some of those who claim to be scientists
| are more akin to politicians than scientists. And if that
| is not your intention, then I would say that is a failure
| on your part to convey what point you actually wanted to
| make.
|
| You want to knock his use of the term "real virologist",
| but he's using it to distinguish the people as people who
| work in virology and not random people on the internet
| arguing about the semantics of an apparently ill-defined
| term.
| throwawaymaths wrote:
| I read it differently. I read it as the gp indicating
| that at the point where they are engaging in political
| play a scientist writ large ceases to be as much of a
| scientist. Perhaps that's not the original intent of the
| [gp], note: edited for clarity
|
| Edit: Oh wow. I just read gp's comment below. It was the
| original intent of GP.
| aliqot wrote:
| What is a scientist in your context? I see the definition
| according to Webster's, does yours differ from that?
| jpeloquin wrote:
| Getting everyone to agree what "gain of function" means is a
| lost cause.
|
| "The term GOF didn't have much to do with virology until the
| past decade. Then, the ferret influenza studies came along. In
| trying to advise the federal government on the nature of such
| research, the US National Science Advisory Board for
| Biosecurity (NSABB) borrowed the term ... From that usage, it
| came to mean any research that improves a pathogen's abilities
| to cause disease or spread from host to host."
|
| https://www.nature.com/articles/d41586-021-02903-x
|
| The actual regulations sensibly avoid the term, targeting
| "enhanced potentially pandemic pathogens".
|
| https://www.nih.gov/news-events/research-involving-potential...
| peteradio wrote:
| Following your link Sars-cov-2 falls under that
| categorization.
|
| > Examples of pathogens that have the potential to cause
| human pandemics, or have caused a human pandemic, include the
| H5N1 or H7N9 influenza viruses(link is external), also
| referred to as bird or avian influenzas, SARS-CoV(link is
| external), which caused an epidemic in several countries in
| 2003, and SARS-CoV-2(link is external), also known as Severe
| Acute Respiratory Syndrome Coronavirus 2, which causes
| COVID-19 disease.
| kodah wrote:
| Not a biologist or virologist. Would it be better to zoom out
| and just tightly regulate anything that studies a virus using a
| chimera?
| beebmam wrote:
| Are you opposed to any kind of inducing of mutations in viruses
| in vitro? What specifically are you opposed to?
| defen wrote:
| I don't even see how this experiment could have possibly
| demonstrated a "gain" of function (in terms of danger) - the
| original Wuhan coronavirus had a 100% fatality rate in these
| mice models. So if they had done this experiment and gotten a
| 100% fatality rate again...what's the conclusion?
| bgentry wrote:
| Making a 100% deadly virus more contagious, or from the other
| perspective, making an extremely contagious virus more
| deadly, certainly sounds like "gain of function" to me. In
| either case the virus under study has been made more
| dangerous / improved on its prior "function", which was a
| likely outcome of the experiment. -\\_(tsu)_/-
| DiogenesKynikos wrote:
| It's very easy to get frightened about virological research if
| one doesn't know much about virology. Viruses are scary.
| Scientists altering viruses in the lab conjures up scenes from
| horror flicks.
|
| Then you read a bit about virology, and you realize that most
| virological research involves altering viruses, and that these
| sorts of experiments are orders of magnitude less likely to lead
| to a super strain outbreak than the millions of people around the
| world who right now have SARS-CoV-2 replicating in their throats,
| and who are walking around maskless, breathing at other people.
|
| If you want to gain a bit of familiarity with virology in your
| free time or during your commute, I recommend listening to This
| Week in Virology: https://www.microbe.tv/twiv/
| [deleted]
| tinus_hn wrote:
| In other news, science can't be expected to know how one can be
| protected from the coronavirus, because it's new and nothing is
| known. However, humans manipulating the virus in a lab is
| perfectly safe and fine and responsible and can in no way lead or
| have lead to the virus escaping that lab.
|
| I'm not quite convinced.
| AzzieElbab wrote:
| marshray wrote:
| No.
| AzzieElbab wrote:
| How about only those making existing viruses more contagious
| and deadly?
| mise_en_place wrote:
| The proverbial genie is out of the bottle I think. Anyone
| with a high school chemistry set can engage in these same
| types of experiments. There are even tutorials for
| biohacking w/ CRISPR on YouTube.
| possiblydrunk wrote:
| Derek Lowe expresses a narrow definition of GOF to make his point
| and defend the research. Interestingly, using his definition, no
| _proposed_ experiment could be classified as GOF because his
| definition depends on a successful outcome where a more
| pathogenic virus is produced which can only be determined after
| the fact. He misses the point that there are various definitions
| of GOF, and more importantly, that the people concerned about the
| experiments aren 't concerned about the precise definition of GOF
| -- they are concerned with experiments that _might_ reasonably
| generate successful GOF mutations.
|
| "In other words, any selection process involving an alteration of
| genotypes and their resulting phenotypes is considered a type of
| Gain-of-Function (GoF) research, even if the U.S. policy is
| intended to apply to only a small subset of such work." [0]
|
| "...experiments that encompass all influenza viruses, SARS-CoV,
| and MERS-CoV that can be reasonably anticipated to increase
| pathogenicity or transmissibility in mammalian species" [1]
|
| [0] https://www.ncbi.nlm.nih.gov/books/NBK285579/#sec_28 [1]
| https://www.ncbi.nlm.nih.gov/books/NBK285579/#sec_30
| [deleted]
| autokad wrote:
| That's how they do, they play games with words. I can imagine
| them making an airborne version of HIV that only kills 80% of
| infected "well its not gain of function because it kills less
| than the original strain"
| VectorLock wrote:
| They will then vehemently defend how important it was for
| them to make airborne hyper-HIV because it will then help us
| understand how to protect us from airborne hyper-HIV.
| gus_massa wrote:
| Does your definition include attenuated virus like the used in
| the oral polio vaccine?
| possiblydrunk wrote:
| It's not my definition. And I can't tell what experiments
| you're referring to, so it's not reasonable to comment. But
| the experiments done at BU had the potential to produce new
| viable virus sequences that could display a phenotype that
| included increased pathogenicity. The researchers had no way
| of knowing what the results would be in advance. They
| followed all safety protocols -- that's not being questioned.
| But their experiments would qualify as GOF experiments under
| a variety of definitions.
| DiogenesKynikos wrote:
| > And I can't tell what experiments you're referring to, so
| it's not reasonable to comment.
|
| Not to be too harsh, but if you don't know about the
| experiments conducted by Sabin that led to the live
| attenuated oral polio vaccine, then you don't know enough
| about virology to comment on the gain-of-function debate.
|
| This is the equivalent of wading into a highly technical
| debate among computer scientists and then saying that
| you've never heard of the concept of a Turing Machine.
| thatguy0900 wrote:
| Gain of function research on dangerous viruses is one of those
| things that seems like such a obviously and totally awful idea
| that I have to assume I'm missing something. Is the whole thing
| just a bio weapons program with a sheen of paint and the
| occasional lab escape is a cost of doing business? Like this is
| stuff that will, eventually, always have an accident, no?
| Especially when it's financed to happen in countries with less
| than stellar working conditions. I can't imagine that everyone
| involved is so deluded as to think they can repeatedly make super
| viruses with no consequences, right? What am I missing?
| StanislavPetrov wrote:
| >I'm missing something
|
| The only thing you are missing is the hubris of the researchers
| involved, typified by the attitude of the author in this piece.
| In my opinion, the preponderance of the evidence available
| today strongly suggests that Covid was indeed created in a lab.
| Countless millions are dead and the lives of billions have been
| permanently upended. The fact is that there is no such thing as
| perfect safety, and there is always a risk that whatever
| viruses they are creating and/or modifying in a lab will be
| released into the wild. These researchers are risking the lives
| of millions with their franken-virus research - which is why it
| was halted by the Obama administration years ago. The
| engineering/modification of dangerous viruses should be
| completely banned with extremely harsh criminal penalties for
| anyone violating this ban. The fact that we are still letting
| these so-called scientists gamble with the lives of millions
| after Covid is an extremely withering indictment on our
| society.
| chubs wrote:
| I was not aware that Obama halted GoF research; thanks for
| informing us. Not generally a huge fan of his, but credit
| where it's due in this instance, this is great! It's a
| tragedy the ban seems to have been rescinded.
| docandrew wrote:
| I'm with you - even if it can increase our "understanding" the
| downside risk just seems too high to me. And what about a bad
| actor? Like the misanthropic scientist from 12 Monkeys?
| lcnPylGDnU4H9OF wrote:
| I believe the idea is that it helps researchers understand how
| better to mitigate negative effects caused by a given virus.
| It's commonly seen (among virologists) as having at least some
| merit.
| StanislavPetrov wrote:
| >It's commonly seen (among virologists) as having at least
| some merit.
|
| The risk of millions dying is not worth the possible benefit
| of gaining better understanding.
| slt2021 wrote:
| yet these lab rats have never created a single vaccine. All
| vaccines are created by a totally different people, who have
| nothing to do with these deadly chimera virus experiments
| XorNot wrote:
| Why do you think scientific research is published?
| yucky wrote:
| To keep that sweet sweet grant money coming?
|
| Well that's not the _only_ reason, but it 's probably the
| biggest if we're being honest.
| slt2021 wrote:
| mRNA vaccine technology is completely different from the
| technology they use to create chimera viruses
| rolph wrote:
| this is recombination, portions of virus are swapped around, in
| this case an omicron spike, with wuhan backbone.
|
| this sort of manipulation can produce gain of function when there
| is interplay between the recombined elements, most often it is
| simply a recombination of functions. to split hairs, the wuhan
| "backbone" [not spike] gained function of omicron spike, but lost
| function of wuhan spike.
|
| gain of function doesnt have to be so dramatic. there is a non
| spike region, of coronavirus that modulates virus/interferon
| signaling dynamics, modification of a small number of, [as in
| 2-3] codons will produce lethality
|
| that itself is not gain of function it is potentiation.
|
| a clear cut case of gain of function would be a recombination of
| wuhan backbone with chimeric SARS-MERS spike that retains both
| target specificities [ACE2-DPP4]
| causi wrote:
| _So this was not a gain-of-function experiment_
|
| So what's the definition of gain of function? Does it have to add
| a function that isn't found in the wild? I'm struggling to come
| up with a definition that excludes this experiment but includes
| everything that _is_ considered gain of function.
| Vecr wrote:
| It's gain of function if the virus gains any sort of function.
| Splicing two viruses that have different properties into one
| that shares at least some the properties from both, even if
| both of the original viruses are natural, is gain of function.
| beebmam wrote:
| I'd recommend deleting or editing your comment. The actual
| definition of "gain-of-function" is quite easy to find if you
| want to take this matter seriously:
| https://en.wikipedia.org/wiki/Gain-of-function_research
| DiogenesKynikos wrote:
| That's not what what virologists mean when they say "gain of
| function." By that definition, almost all lab virology would
| be considered "gain-of-function." If you strictly regulated
| that, virtually all virology research would grind to a halt.
|
| The gain-of-function debate began in the 2010s over a
| specific set of experiments that were done on influenza. The
| term is used to describe changes that render a virus that has
| the potential to become a pandemic more virulent or more
| transmissive.
| peteradio wrote:
| Sars-cov-2 is already a pandemic causing agent.
| docandrew wrote:
| Yeah to me the definition seems dependent on the experimental
| results. If the experiment succeeds in creating Captain Trips,
| it was GoF. If not, it wasn't?
| rolph wrote:
| modifying the potency of a function is not gain or loss of
| function.
|
| GoF is aquisition of a new tool or capability.
| factsarelolz wrote:
| Kindly follow the science.
| slt2021 wrote:
| if one of these chimera viruses leaks - you can easily sell
| vaccine for $1000 per shot.
|
| Easy money printing machine: keep making new viruses, keep making
| new vaccines, make $$$
| webdoodle wrote:
| Its bioweapons testing, and it is a crime against humanity.
| gweinberg wrote:
| Similarly, it wasn't Russian Roulette because the chamber the
| hammer fell on wasn't even loaded!
| [deleted]
| chatterhead wrote:
| Here is the musical version of this author's argument.
|
| https://www.youtube.com/watch?v=a-1_9-z9rbY
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