Similar story here : Hunting my sonâs killer
⌠We live in interesting times.
Does knowing make it easier for these parents? I guess our human tendancy is to blame ourselves for something we imagine we might have done when we donât know.
The costs of these genome analysis just keep dropping so we are rapidly getting to a point where we can help couples make informed choices about risks even before they have kids. Amazing work.
I wonder how good the tools are getting at searching out the mutated chromosomes. Perhaps when the accuracy rates of the exome sequencing drops (and/or full genomic sequencing eventually) and the costs drop to zero (its on the way!) will we really start to see revolutions in medicine.
It just goes to show how little the Human Genome Project and Hap Map have yielded that itâs still a huge puzzle to track down a disease caused by a single gene. These projects were supposed to let us solve complex multigene diseases. While itâs nice to have the fancy hardware that can do the DNA profile for this poor family, the HGP probably did not contribute much. And this is done using trio data (parents and offspring), so itâs not like the HGP and HapMap data at all. In fact those projects were supposed to make trio studies obsolete.
BTW, they concluded that the problem is an autosomal recessive lethal mutation and both parents are carriers. They said it was a 1 in 64 chance of three children in a row getting it (which implies the twins were fraternal), which would be 0.250.250.25=0.0156. Although that seems like a bit a stretch, itâs also the odds of flipping a coin and having it come up heads six times in a row
That simply isnât true.
The HGP was certainly overhyped in its day, but I donât think any serious medical or scientific expert honestly believed that a single, crude composite genome sequence would answer most (or even many) of lifeâs mysteries. What it has undeniably done is offer a valuable framework - a lay of the land against which other genome sequences can be organized and understood and compared. Every new set of genome sequence data is composed of zillions of short 100 to 300 nucleotide âexcerptsâ that are meaningless unless scientists have a clear sense of their proper coordinates in the genome. HGP and HapMap also gave starting points for understanding sites and combinations of common variation, but by definition rare diseases are RARE, and will therefore need a family-based trio sequence analysis.
TL;DR version: Without the expensive, first-of-its-kind work done in the HGP (and the parallel efforts from Venter et al.), there would be no personal genomics - just like there had to be a Sputnik before there could be an International Space Station or GPS satellites.
The bioinformatics community certainly âbelievedâ it in a sort of group make-believe that ignored variation in chromosome size and copy number. The cytogeneticists knew this, but the statistics folks were doing their usual scoffing at the very notion of empirical knowledge. We ended up with a repeat of how microarrays were going to be the answer (that statisticians all promised), and that was about the same time we were being told that massive NMR would prove protein form predicted function ( well that lasted about 3 months), and thereâs a couple more that will occur to me.
All of these supposedly transformational technologies are driven by the need for large hardware vendors to get the government to splurge on billions of dollars of hardware and reagents. And before anyone realizes itâs 95% hype, weâve moved onto the next fad.
Every shiny new technology goes through a hype cycle, but itâs silly to follow the backlash all the way back the other way and devalue what those technologies have actually delivered. These are in fact transformational tools, and just because Time and Newsweek (and ok, maybe occasionally Nature) promised us jetpacks doesnât mean we arenât reaping real benefits in terms of disease diagnostics and our understanding human biology. Much as it pains me to quote Rumsfeld, there will always be âunknown unknownsâ. If youâre clever enough to look past the hype, then you shouldnât be disappointed when things turn out to be a bit more complicated.
Sequencing IS in hospitals, and being used to guide patient care (see for example Baylor and UMichigan, or Foundation Medicineâs cancer platform). Microarrays are in fact routinely used for patient diagnostics and identifying new disease genes. All these new technologies and reagents? Theyâre still being used, not rotting in an alley. Read the Methods section of any journal article - lots of equipment and tools from 10 years ago is still routinely used. I donât understand the need to piss on these kinds of concrete advances just because weâre not living in Star Trek yet. It reminds me of that Louis CK routine about how everythingâs terrific but nobodyâs happy.
How about Francis Collins?
[quote=âTheBaron, post:7, topic:27632â]
It reminds me of that Louis CK routine about how everythingâs terrific but nobodyâs happy.[/quote]
The people who can surf these waves of hype are extremely happy, the people whose research programs got slashed so administrators could buy expensive toys, not so much.
The vision was a factory style research culture where scientists were obsolete. The pharmaceutical industry lost the better part of a decade after slashing and burning their research units. They ended up with empty drug pipelines. They had to turn back to working with academic scientists who still knew things, like Irish monks who rode out the Dark Ages on remote islands.
Do you have a particular quote youâd like to cite? Even the experts can be loudly wrong about their own area of expertise, like that famous chestnut about Thomas Watson thought the world only needs five personal computers at most.
And people arenât getting their research programs slashed so that they can buy a new machine from Illumina. Theyâre getting their funding slashed because of an ignorant Congress that doesnât value scientific research and squabbles like children over every single budget negotiation. Again, please provide quotes about this âvisionâ - smacks of a strawman to me.
Regardless, my point still stands. Maybe you donât like the hype, but that doesnât mean that geneticists and biologists havenât made amazing progress with those very tools.
EDIT AT 12:12p: I would respond further in this discussion, but because Iâm a n00b to the board Iâm restricted to three replies per post. But in parting: thereâs no logical fallacy in my post - if there was no money poured into the HGP and (to a lesser degree) HapMap, then yes, we would absolutely be considerably more ignorant about human biology and genetics, and would lack the skills, knowledge and technology to move medicine forward. Was everything as efficient as I would like it to have been? Hell no. What big program (public/private/academic/nonprofit) is? Was it worth the money? Hell yes.
Missed your edit about the HapMap commentary, will look into that - but again, these research efforts were all valuable building blocks even if they werenât universal solutions. Iâm not here to champion Collins or say he never put his foot in his mouth. Iâm making a bigger point about the value of the technology once you get past the hype.
The fact is, academic scientists who are âsaving the dayâ (per your post above) from âdumb pharmasâ who wasted their money are among the biggest champions and early adopters of these genomics technologies and the big corporations that are reluctant to move into this area. What do you think these academic scientists are doing, sequencing DNA by hand? Figuring out protein structures with a pencil and paper? I worked in an academic bio lab in the 90s - trust me, I would have killed for a modern genome sequencing platform, and so would every single person in my department.
[quote=âTheBaron, post:9, topic:27632, full:trueâ]
Do you have a particular quote youâd like to cite? Even the experts can be loudly wrong about their own area of expertise, like that famous chestnut about Thomas Watson thought the world only needs five personal computers at most.[/quote]
Iâde refer you to Terwilligers & Hiekkalinna .âAn utter refutation of the âfundamental theorem of the HapMapââ ( An utter refutation of the "fundamental theorem of the HapMap" - PubMed ).
When Collins wrote the paper wrapping up the hapmap he promised to answer these criticisms in his paper, and then he didnât.
There was supposed to be a fixed framework that was going to apply to everyone - this is what was sold to the politicians, and the scientific community knew it was bs. The statisticians filled their usual role of claiming that whatever the data looked like theyâd be able to fix it with some sort of opaque mathematical voodoo. and anyone that doubted them must be dumb.
Youâve constructed some sort of logical fallacy there - that nearly 20 years and billions of dollars would have produced nothing had it not been poured into the HGP and HapMaps.
You probably want to pick a better example.
Iâm not being a Luddite about the technology - Iâm criticizing the idea that scientists would be largely redundant in an era where science would consist mostly of vendors dealing with administrators.
And why didnât your department have sequencers? because people would have been sequencing stuff that directly interested them instead of following the lead of the HGP committees. They got to act as gatekeepers.
Oh, the other fad that ended with a thud was ontologies, which are sort of still around, but they gave up on the formal magical definition of âontologiesâ and are now really talking about controlled vocaularies, which they used to ridicule.
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