I will admit to not understanding this post.
I find that adults who were only children are a trial to live with.
2: Adults are a trial to live with. Children too.
Our household is ENTIRELY COMPOSED of only children. So many resources showered upon so few!
I will admit to not understanding this post.
Really? It's two entirely unrelated points. Is that throwing you off?
4: Uh, there definitely was no intended insult.
1: I think it is arguing that epigenetics provides a significant new opportunity for over-interpretation and generalization similar to veldt-y explanations. People raised by assholes act like this; other people act like *this*--because methylation.
I was just thinking that perhaps young children, in another universe, might have traits which made them easier to get along with, but in our universe, they were selected for traits that made them difficult to get along with, so that we didn't try to take on too many of them at once.
Sometimes blog posts are hard to understand, but that's because they were produced by a neural mush.
Epigenetics poised to become the new folk explanation of why you had your bad luck coming.
is confusing?
5: the first point I think I got. The gist of the second point -- that epigenetics will be used by rich white men to justify their worldview -- I got. The meat of the second point -- why or how this should be so -- evades me. And the line about neural mush baffles me completely.
It's not surprising that epigenetics exists within in a person's lifespan. However, it's neat that we now understand how it works, better. That's the third paragraph of the OP.
The sensationalism seems to be extending it across generations, for which there is very little evidence, but the author is really excited about. That's the broader point.
8 sounds veldt-y to me.
Young children are difficult to get along with because they demanding of resources and reassurance. They're demanding of resources and reassurance because they can't get them for themselves. Show me a planet where children are as precocious as deer or something and I'll show you children who are a lot less effort.
"Neural mush" is just because I didn't feel like saying things using the wrong vocabulary and getting hassled. Neural connections? Neural chemistry? I dunno, those all sound right to me, but it's all a big mushpot up there to me.
14 is taking a humorous point waaaaaaaaay too seriously.
And the line about neural mush baffles me completely.
I like fried neural mush. Just like Mama used to make.
The sensationalism seems to be extending it across generations, for which there is very little evidence
Wait, what? I haven't read the article, and maybe I'm poorly-informed, but I thought there was uncontroversial evidence that certain epigenetic changes are inherited in certain conditions. In mice, at least, but also maybe in humans from things like the Dutch famine study?
Maybe this thread will be more enjoyable after the resource-drainers have been deposited at daycare, and my methyls have been properly caffeinated.
I haven't read the article
In the article, the editor is very sensationalistic about things that are unsupported by the content of the article, which is notably reserved.
I like fried neural mush. Just like Mama used to make.
or that stuff in neural mush tamales? Mensa?
I assume you've seen the link on only children that's been going around FB.
"a genome-wide analysis of blood samples taken from 40 men who participated in a British study of people born in England in 1958."
The whole point is that methylation is tissue specific so why should blood samples indicate anything useful?
"The offspring did not show most of the behavioral abnormalities, suggesting that epigenetic transmission may not be at the root. Instead, Nestler proposes, "the female might know she had sex with a loser. She knows it's a tainted male she had sex with, so she cares for her pups differently"
That's the kind of evidence free speculation I've come to expect from pop science.
When losers have sex, sex will only result in losers.
I like fried neural mush. Just like Mama used to make.
Scattered, smothered, and covered.
It's very high in cholesterol.
I saw somebody complaining about processed baby food and one of their reasons was that it was high in saturated fats. But that's what you need to make a brain.
Can't we just recycle brains from people who aren't using theirs any longer?
Then we can have inheritance by prion and do away with the whole nucleic acid thing entirely.
You should get tested, your reaction time is slow.
I always worry about giants holes in my brain.
18: It depends on what you mean by "trans-generational." The work you're sure you've heard about is about inheritance between generations 0, 1, 2. If you take the term to mean inheritance lasting longer than that, there's some work, none in humans that I know of.
24: I didn't read the links so I don't know what you're quoting, but if the study was about a psychological question: brain tissue is hard to get, so researchers look at blood. Whether that's going to wind up being meaningful at all is an open question.
It's page 3 of the linked story about mark changes in poor vs wealthy children from mid 1900s. Of course it's easier to get blood than brain from 1958, which is fine if you're studying sequence, but when you're studying something you're explicitly claiming is about chemical exposure in particular tissue types you need to justify why a different tissue is at all relevant. Maybe the scientist knows that but of course the popsci author is going to ignore the distinction.
34: I don't think scientists do know it. As far as I understand, they're just taking an available proxy for unavailable tissue and hoping they'll find an interesting relationship between epigentic changes and phenotype of interest. Then if they do, presumably they'll move on to post-mortem studies. It's definitely worth critiquing.
Imprinting is deterministically heritable. Anything else? Not as far as I know.
It's a cool mechanism, but good experiments are difficult to do, and apparently also to design if this what's getting done.
Our household is ENTIRELY COMPOSED of only children.
I've met you and snark and consider both of you adults. Don't listen to whoever's been putting you down.
Related, Myriad patents unanimously struck down. Good result.
Shares in Myriad fell sharply on the news...
I haven't read it yet, but in general, great!
Surprisingly: "Myriad rose $2.91, or 8.6 percent, to $36.83 at 10:35 a.m. in New York."
This is a little odd from Scalia:
JUSTICE SCALIA, concurring in part and concurring in the judgment.
I join the judgment of the Court, and all of its opinion except Part I-A and some portions of the rest of the opinion going into fine details of molecular biology. I am un-able to affirm those details on my own knowledge or even my own belief. It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state; and that complementary DNA (cDNA) is a synthetic creation not normally present in nature.
Dude, it's really not that complicated, especially the HS level summary he's referring to that ignores any of the caveats of the process.
On the veldt, expectations get priced into the market. Or something.
42: Again, I haven't read the opinion, so I can't speak to exactly what he's addressing. But I like the idea that he's saying "I don't need to affirm that bit to join in the ruling, and I am willing to say that my knowledge of this area is weak enough that I can't rely on my judgment for the accuracy of a technical explanation." Not thinking that way -- that is, judges thinking they understand things they don't -- seems to me to be the basis of a lot of bad patent law.
1A is the really basic scientific summary- DNA consists of AGCT. It is transcribed to pre-mRNA where U substitutes for T. Pre-mRNA is spliced to mRNA and that is translated to proteins. We can artificially convert spliced mRNA back to cDNA using lab techniques. Sometimes the sequence changes and these are called mutations.
Since it's Scalia I'm looking for some underlying trick, the part about "my own belief" reads like "well, sure scientists tell us that's what's happening, but I've never seen it myself so I don't know if it's real, just like evolution and global warming."
41. They must have expected them to strike down the whole house of cards. But this:
Writing for the court, Justice Clarence Thomas said isolated DNA is a "protect of nature and not patent eligible merely because it has been isolated."
||
My weird former student keeps using "#nofilter" on her statuses to express entirely innocuous things, like "My son turns four months old today!" and "Daddy with baby!" photos.
42 -- Without having read it, that may be one of only a very very few Scalia opinions I can wholeheartedly endorse. Appellate fact finding is way way way out of control, especially on the Supreme Court. Appellate should be limited to the record and record evidence, not making broad pronouncements about what is and isn't good science (or, more normally, what the facts are) based on their own understanding. Of course, as is typical, Scalia himself is usually one of the worst offenders.
47: Maybe the photo was of the mailman and the baby.
47: Everything is meaningless on the internet. A friend tells me that his announcement on Twitter that his mother's play was being produced somewhere was greeted with "check your privilege!" People hear something and start using it indiscriminately.
How many comments will respond to 51 with "check your privilege"? I wonder!
I wonder how many people say "check your privilege" instead of "your fly is undone"?
That's when "no filter" would actually make sense.
As a head's up, I mean. "Dude, your shlong is unfiltered. Check your privilege."
I wonder how many people say "check your privilege" instead of "your fly is undone"?
I usually go with "examine your one-hole context".
A friend tells me that his announcement on Twitter that his mother's play was being produced somewhere was greeted with "check your privilege!"
That's awesome.
58: I don't know who might have a Prince Albert.
49: Of course, as is typical, Scalia himself is usually one of the worst offenders.
Yeah, can't wait to see what he gets up to in the VRA case. (God, I would like it to be in dissent--but I have little hope. I'm finding the prospect unusually depressing, or maybe I'm just projecting unrelated feelings on to this particular outcome.)
49 -- Section I-A really does read like a high school level summary. Even I can understand it.
"Respondents state that racism exists and one manifestation is the restriction of voting rights. I am unable to affirm those details on my own knowledge or even my own belief. Reversed, bitches!"
Here's where i reveal my age/out-of-it-ness*. I have no clue what #nofilter on a Facebook status would normally convey. (Unvarnished truth in some manner evolved from "unprocessed" photos?)
*At least with regard to Facebook, I guess.
Using hashtags on Facebook conveys idiocy, I think.
Also noted that section 1A gets it right (complimentary DNA = cDNA) but the summary of the decision flubs it as "composite DNA (cDNA)."
Also not addressed- if you have a gene that does not have exons, can the cDNA be patented (or if you make cDNA of just one exon?) Because in that case the cDNA matches the genomic DNA, but by referring to it as cDNA it would seem to fall under the part of the decision that says cDNA patents are valid.
Using hashtags on Facebook conveys idiocy, I think.
I like Facebook because I can see which of my old high school classmates are still/now hot.
Shit, complementary DNA.
All my DNA thinks you're great.
64: I assume it usually means over-sharing. TMI.
I don't follow the cDNA portion of the opinion. If I understand correctly the information content in the cDNA is identical to the information content in the mRNA which is a part of nature. Obviously the process of converting between mRNA and cDNA would be patentable (except that its already well-known), but how can you patent the product when it's just performing a well understood manipulation on a product of nature. Are they saying that you can't patent the isolated DNA itself but you could patent the string of symbols used to encode it in the relevant computer language (there must be some standard software used by geneticists to store DNA sequences).
They're saying you can patent the physical cDNA because such a construct does not exist in nature (it is chemically distinct from the naturally occurring spliced mRNA.) So if you have a sequencing/analysis process that uses that cDNA as an intermediate they can block you from using that process. Fortunately there are lots of workarounds.
"Are they saying that you can't patent the isolated DNA itself but you could patent the string of symbols used to encode it in the relevant computer language"
No, you can't patent the information content, just the physical cDNA entity.
It sounds stupid to me, admittedly.
Obviously the process of converting between mRNA and cDNA would be patentable (except that its already well-known),
This seems exactly right,
but how can you patent the product when it's just performing a well understood manipulation on a product of nature.
And so does this.
I mean, surely someone could create a cDNA version of the whole genome, and patent the whole thing tomorrow, right?
I mean, surely someone could create a cDNA version of the whole genome, and patent the whole thing tomorrow, right?
Right. And if you were named "Art," both you and the cDNA version of you would then be Prior Art.
70: It's an Instagram thing: "I didn't apply one of their color filters to this pic." It's kind of expanded from there, though.
"surely someone could create a cDNA version of the whole genome"
This is a slight concern for me, because there are processes in which you're analyzing other genes in which cDNA of all genes is initially made in small amounts (called oligo dT priming.) It would be pretty ridiculous to say you can't use those established processes without permission from every holder of a cDNA gene patent, but the law is brilliant in its absurdity.
Ah. Maybe the student was using it correctly, then.
I really don't know much about epigenetics. But 73 is right. The process of turning RNA into cDNA is already patented. When you buy this the manual contains a bunch of unreadable licensing mumbo jumbo, just like when you buy a DiscMan.
Yeah, fine, random priming works too.
That particular company happens to be one of the pretty nasty vultures about enforcing their patents too, no qualms about going after academics.
Say one day we have DNA computers. Can I patent the DNA molecule implementing quicksort? It's a new synthetic molecule!
CYP PDQ
I don't know who might have a Prince Albert.
We should totally call leather bars and when someone picks up, say "do you have Prince Albert in your eurethra?" and when they say yes, yell "WELL LET HIM OUT!" and then hang up.
Or what about isotope labelled versions of isolated DNA? Same information content, built by a well-known process, but it's a synthetic molecule!
81: I briefly tried for an "in the can" joke, but would certainly have not come up with that one.
Also, it suggests to me that the cDNA patent is trivially evadable. The information in a gene isn't patentable, because that's nature. So the cDNA patent must cover something much more like a copyright -- the literal sequence of bases. If the patented sequence is TACGCCTGCAACACGG, I can't see an argument that TACGCCT-synthetic intron that can be successfully disregarded when using the gene--GCAACACGG violates it.
cDNA copying seems a lot like like violating "copyright" than violating a "patent". You know how 50 times a day, every Kinko's location undergoes the following exchange.
"Sorry, I can't make copies of this."
"What?"
"Unless you have permission from the copyright holder."
"What?"
"This is copyrighted material."
"What?"
"Have a good day, sir."
"What? I'm not allowed to make copies of this? How is that possible?"
"Next customer please."
Wikipedia would probably tell me this, but is there any historical evidence that Prince Albert had a Prince Albert, and if so, how does that work? Was there a lot of genital piercing at the time?
Not understanding the example in 85. The cDNA is the sequence without introns. Also not so easy to make random synthetic introns that will splice out correctly.
88: Somehow I suspect googling "Prince Albert" at work is going to set off your Net Nanny.
Oy, that moment where you click yes on a friend request from someone you last talked to in the 80s and see:
One of these days He will wake up and see, even though you tried to make my life horrible....God said "NO Sir"! She is blessed by me. And because she is blessed, her seed is blessed. I may seem like you are winning, but MY God has the final say!I told you before, and I will tell you again.....It's the Blood! You better get you some!
My last status update is about the cough syrup bottle giving me stigmata, so this should resolve quickly.
I might be back later with some potentially dumb questions on the epigenetics, but have had a fine time reading up on the Hayflick Limit, telomers, telomerase and apoptosis. You know, you don't need to contemplate something like the eye to boggle at evolution, the eye is a relative piece of cake compared to the internal workings of every fucking living cell everywhere.
Presumably there's a way to chop small bits off the ends of mRNA? If so, you first do that and then run that through reverse transcription. Now you have a "new" synthetic molecule without breaking their patent. (But you can't first do reverse transcription and then chop off the ends, because that would be breaking the patent.)
88: These apocryphal tales--which included the notion that Prince Albert invented the piercing that shares his name in order to tame the appearance of his large penis in tight trousers--are widely circulated as urban legend. No historical proof of their veracity has been located independent of Malloy's assertions.
Did not realize that the specific genes involved were BRCA.
89: Right. So the sequence without introns is patented. The same sequence (with some random intron that I handwavingly assume you can work around somehow) isn't. It doesn't matter that they're meaningfully the same thing, because the sense in which they're meaningfully the same is the same sense in which they're both the same as the original sequence which isn't patentable.
Ok, so you could make that without violating the patent, but why would you want to? The artificial version you've made would never be used in a diagnostic- Myriad is focused on making cDNA from human samples (which likely lack the LB sequence) to analyze for mutations. They can block others from using the same process because part of the process involves making the patented cDNA.
Now you could intentionally introduce a meaningless mutation in the reverse transcription step that generates the cDNA (using a mutant primer) so that your resulting cDNA is different. Still no introns, but with a meaningless mutation you've put in to bust the patent while still being able to analyze the physiologically relevant part of the sequence.
Now you could intentionally introduce a meaningless mutation in the reverse transcription step that generates the cDNA (using a mutant primer) so that your resulting cDNA is different. Still no introns, but with a meaningless mutation you've put in to bust the patent while still being able to analyze the physiologically relevant part of the sequence.
Right, that sort of thing, except that I had no idea what exactly Myriad was doing.
Focusing on point nucleotide differences of the product is missing the point, I'm pretty sure.
The Myriad patent covers sequencing your personal copies (2, one each from mom and dad) of the genes BRCA1 or BRCA2. cDNA gets made from your genome, which may have variations from the version of the genes in the reference sequence. These variations (either point differences, rearrangements, or big missing pieces) can have clinical relevance. To do this extraction via cDNA and then sequencing, particular PCR primers are used.
Anyone trying to use these primers (or I guess neighboring primers) designed from the publicly available sequence would have been infringing Myriad's patent. I haven't read their patent in detail, not expert, but basically they had exclusive rights to chemistry registered with the FDA that allowed company and patient to see just what the patient's version of the gene was. Designing that chemistry and getting approval to use it clinically required understanding the reference genomic sequence.
But the information in the reference sequence is all in the unpatentable natural sequence with the introns. So the patent has to be (again, this is unprofessionally argumentation, I don't know what I'm talking about either legally or technically on any detailed level) limited to only the literal 'reference genomic sequence' Myriad patented (as opposed to all possible sequences that would contain the same useful information, but also other stuff). At which point, what keeps anyone from starting from the natural DNA, running whatever process Myriad uses to generate cDNA, except doing so in a way that also incorporates a certain amount of disregardable nonsense? That's then an unpatented reference genomic sequence, and using it it should leave you in the clear.
That this might work is idiotic, but it's only idiotic because the patent is idiotic.
99. My understanding (which may be wrong as to legal substance or contents of the patent) is that Myriad's patent covered in part the knowledge that "BRCA1 starts at nucleotide x of chromosome 17, exon 1 extends 151 nt...." or the equivalent. This knowledge was publicly funded and in the refereed literature. Myriad designed a test using public knowledge that many thousands of competent biochemists could have done also, and then took that test to the FDA so that they could sell it claiming clinical relevance. To protect their investment, they filed an (IMO) overly broad patent.
Tangentially, reading patents is a bitch, much worse than reading papers. They're written in what amounts to code that's purposefully obscure. I skimmed this patent once years ago, have not reread it, and then read third-party interpretations of what the patent contained. My perspective is that I understand the biology, not the contents of the patent. But the patent is definitely intended to prevent anyone else from doing equivalent biochemistry with slightly altered primers.
I certainly don't know what I'm talking about, and haven't even read the opinion. But I thought the Court had struck down the patent insofar as it purported to patent the gene as it exists in nature, and only left intact the patent on the literal sequence of cDNA prepared by Myriad from the naturally existing DNA. So the knowledge you refer to would be the part of the patent that didn't survive today's ruling, and using that knowledge to create an alternative to Myriad's cDNA would be okay.
Maybe I should say that I'm pretty happy with the decision, it should not cost thousands to apply commodity biochemistry to your genome.
I don't know what the best legal regime for protecting a company's investment in clinical trials would be, and I've thought about it. Clinical trials are risky and they have a high fixed cost.
Okay, I just read the opinion, and the bit that upholds the patent for cDNA is really stupid. All it says is that the cDNA is 'new', without any meaningful discussion of whether it's 'non-obvious'. If I understand what people are saying, once you have the natural gene, generating cDNA from it is absolutely obvious, meaning that it shouldn't be patentable.
103. Basically. There are a lot of details-- thermostabilizing reverse transcriptase so that it's less likely to fall off is difficult, for one. Companies that sell the biochemistry to pharmaceutical companies have complicated agreements where the chemistry company can retain rights to insights gained using their magic reagents. But from a distance, generating cDNA in simple cases is mostly an application of public knowledge.
Companies that tell biochemistry to universities just harvest email addresses from papers and spam the fuck out of everybody.
100: They're written in what amounts to code that's purposefully obscure.
I hope to be writing a patent in the near future. I love the gobbledygook language. I once got the chance to use the phrase "having a plurality of such bosses severally disposed thereon," which pleased me immensely.
103 -- the decision doesn't discuss the obviousness prong of patentability at all, because that wasn't at issue in the case. The only legal issue was the judge-made doctrine that you can't patent a natural phenomenon or law of nature. That is very very distinct from the obviousness issue.
My personal view (and I'm not a patent lawyer and try to stay as far away from patents as I can) is that the best option for judicial reform of the patent system would be to make obviousness (which is now basically a total non-issue in patent law, since there's effectively a controlling presumption that if you have a novel invention it was non-obvious) a much much much harder hurdle to clear. My understanding is also that this is how it worked before the creation of the Federal Circuit, and district judges would routinely invalidate patents for obviousness before the 1970s. Which is part of why the Federal Circuit was created in the first place. But, in any event, whatever the merits of that separate discussion, obviousness was completely not at issue in this case.
The Supreme Court has come up with a new regulation banning demonstrations on its grounds.
Fast work. I can't help but associate it with the coming big reveal/confirmation that as a body they net out as bigoted, racist fuckheads.
But, in any event, whatever the merits of that separate discussion, obviousness was completely not at issue in this case.
In retrospect, though, it should have been. I suppose it wasn't because no one was expecting the Court to split the baby as it did. Once the Court did, though, surely it was responsible for remanding somewhere to see if the cDNA met standards for patentability generally once the natural DNA didn't, rather than just saying "the cDNA doesn't have the specific problem the natural DNA did, so let's assume it's fine!"
Or, anyway, a new plaintiff should be filing a challenge to Myriad's cDNA patents as obvious, given that there wasn't a ruling on that point.
"Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations."
This is the main thing that makes claims hard to read. There are other issues as well related to the desire to keep claims as broad as possible. "at least one of" "first element" "second element". Also some language used to wiggle around court rulings or magic words. "comprise" versus "consist" . Plus, extensive use of weasel words to prevent the specification from being used to limit the claim.
Patent attorneys would actually prefer the the claims to be easy to read. Most of the time. Plus communicating ideas clearly is hard.
The use of the word "said" is pure jargon though.
"since there's effectively a controlling presumption that if you have a novel invention it was non-obvious"
This isn't true. It is often pretty hard to get an invention to be considered non-obvious at the patent office. The supreme court also recently strengthened the obviousness requirement.
The real issue is why should we give a monopoly for an idea just because it is non-obvious.
Lander just spoke here about his view of the result. Apparently he was name checked by Breyer during oral arguments which he was all giddy about.
Regarding two issues raised upthread:
-Incidental creation of cDNA: might be litigated, but good luck to Myriad or others enforcing that.
-Inserting random mutations, end modification, etc. to bust the patent: Apparently Myriad not only patented BRCA1 but every 15 base or greater sequence possible from the gene. Specifically, "any DNA fragment of chromosome 17 that contains at least 15 nucleotides of the region containing the BRCA1 gene. "The Lander amicus pointed out that since this includes 15, 16, 17...all of chromosome 17, which includes ~10^15 possible fragments. So that claim anticipates your mutation strategy but is likely invalid for being too broad.
Wouldn't that also be invalid as being natural? Any sequence that's uninterrupted by an intron in nature (not that I'd know, but I'd guess most 15 base sequences would be uninterrupted) wouldn't be patentable cDNA, it'd be natural DNA.
Well, 4^15 does give you single genome specificity (one trillion possible sequences) which is probably why that number was chosen. But of course genomic sequences are not randomly distributed.