
The genomic era arrives, and this time is probably real - tosseraccount
http://www.economist.com/news/science-and-technology/21698229-genomic-era-arrives-and-time-its-probably-real-encore-une-fois
======
bognition
I kind of hate articles like this. They feed into the myth that single event
cause revolutionary changes in the way the world works, when it reality its
thousands of evolutionary events that cause change.

I'm not trying to belittle recent advances in genomics, on the contrary I
believe that cheap sequencing and technologies like CRISPR are going to change
the world. However, its the insinuation that the last 20+ years of hard work
were a fraud that upsets me. We wouldn't be were we are now without the last
20 years of genomics research. /rant

~~~
toufka
Exactly. Imagine being a student given a tome of knowledge called something
like, 'Principia Mathematica'. Upon receipt of the book you say, "I will soon
be able to make engines efficient, structures solid, understand the planet's
rotation, and make mathematical models precise." Then two days later someone
asks how to draw up plans for a rocket ship to the moon. You'll get there, but
you have to read the text first, then you have to understand it, then you have
to experiment with it, and then you will (go to the moon). Nothing in your
prediction was unrealistic, but it takes time to learn.

A few decades ago ago we read our first line of source code from a computer
from the year 2,000,000,000 - some pretty advanced technology that was just
handed to us. Two decades ago we did our very first read-through of an entire
human. The reading itself was not particularly productive. We already knew
some of the most important lines of code, from the decades before, and we
annotated a lot more sections that are critical for basic function. We've even
traced a few bugs back to the source code - especially those bugs where 1) the
source was unusually easy to read [1], or 2) the bug was really bad [2]. As of
this year we've developed compilers to enable us to write and run small,
multi-line programs of our own composition [3]. We're doing really well in
trying to read, comprehend, manipulate, and act on some of the most
sophisticated technology ever presented to us. More sophisticated by orders of
magnitude than the silicon in Nvidia's new graphics card (16nm 2d dry feature
size [4], vs 0.1nm, 3D wet feature size [5]) . Reverse engineering it takes a
bit of time, and yet we've already put that knowledge to significant use.

Further, once we do get our working knowledge up and running there will be a
significant outpouring of function from having reverse-engineered such
technology. But of course there is a lag time in the millions of lab-hours
being poured into understanding that technology before we can actually use it.
Not dissimilar to the rapid advances in science-fiction when a race reverse-
engineers an advanced alien technology. How long did it take us to build The
Machine in Sagan's 'Contact'? We will not _just_ cure cancer, but we will be
capable of all sorts of new feats. Purchasing the textbook doesn't make one a
master - it's the study, the hard work, and the practice.

[1]
[https://en.wikipedia.org/wiki/Human_papillomavirus](https://en.wikipedia.org/wiki/Human_papillomavirus)

[2]
[https://en.wikipedia.org/wiki/BRCA_mutation](https://en.wikipedia.org/wiki/BRCA_mutation)

[3]
[https://news.ycombinator.com/item?id=11417689](https://news.ycombinator.com/item?id=11417689)

[4] [http://wccftech.com/rumor-nvidia-pascal-
gtx-1080-gddr5x-gtx-...](http://wccftech.com/rumor-nvidia-pascal-
gtx-1080-gddr5x-gtx-1070-f-gddr5/)

[5]
[https://en.wikipedia.org/wiki/Resolution_%28electron_density...](https://en.wikipedia.org/wiki/Resolution_%28electron_density%29)

~~~
fluxquanta
The idea of lone geniuses single-handedly bringing upon revolutions in science
and tech doesn't help, and it's perpetuated by our culture. Nobody thinks of
the leagues of engineers or doctoral students or fellow "no-name"
professionals who also do a lot of the work. It's really sort of fascinating
how we idolatrize singular people who themselves will admit they were standing
on the shoulders of giants.

------
tosseraccount
The National Human Genome Research Institute keeps an up to date website on
the costs of sequencing: [https://www.genome.gov/27541954/dna-sequencing-
costs/](https://www.genome.gov/27541954/dna-sequencing-costs/) Their "cost per
genome" image suggests the $1000 genome :
[https://www.genome.gov/images/content/costpergenome2015_4.jp...](https://www.genome.gov/images/content/costpergenome2015_4.jpg)
.

The costs of assaying a genome has dropped from $100 million to $1 thousand.

Identifying correlations with clinical metadata, understanding the post
translational interactions and understanding the full roles of proteins and
other molecules remains an intimidating and difficult job.

~~~
themartorana
$1000 is a drop in the bucket of a normal hospital bill or lifelong drug
prescription for advanced/debilitating/catastrophic diseases.

Edit: I realize it's a small part, but it's the first step, and it's already
relatively inexpensive, which is a good sign.

~~~
mbreese
The $1000 is also minor compared to the computational and personnel costs
required to interpret a clinical genome. It's almost cheaper to re-sequence a
genome than store the raw data long term. And the interpretation of the genome
usually requires a multi-disciplinary team with advanced degrees (MS/PhD/MD).
That part of the problem is still largely a manual process, and will be for
the foreseeable future.

I'm not saying that it's not worth it in some cases, but the sequencing is
only a small part of the overall costs.

~~~
tosseraccount
The real cost of sequencing: scaling computation to keep pace with data
generation :
[http://genomebiology.biomedcentral.com/articles/10.1186/s130...](http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0917-0)

~~~
mbreese
But at least scaling computation / storage is possible. A challenge to be
sure, but it's a challenge that the entire computer industry is dealing with.

Interpretation, on the other hand, is quite different. Currently,
interpretation still requires a human to look at everything. And regardless of
how good annotations and algorithms get, I have yet to hear of anyplace where
the final annotations aren't manually curated (maybe automated, but still
requires a human in the loop). This aspect of Precision Medicine doesn't scale
quite as well as sequencing or computation...

------
aclimatt
If you're interested in genomics, you should take a look at the
pharmacogenomics knowledgebase from Stanford:
[http://www.pharmgkb.org/](http://www.pharmgkb.org/)

It is a comprehensive database of dosing guidelines, drug labels, and
annotations for thousands of combinations of genes, variants, drugs, and
diseases.

(We're actually helping them with a redesign, and if you'd like to be a beta
tester, contact me.)

~~~
pat_space
Link to contact?

~~~
aclimatt
Oops, thought it was in my profile. Shoot me an email at matt@bitmatica.com

------
fitzwatermellow
I'd like to see the cost of bioinformatics cloud computing come down by
several orders of magnitude as well. The ideal scenario seems to be a global
network of in-field mobile clinical units that can collect samples, run
diagnostic tests and sequence genome data. Then upload that collected real
time data to public data stores on AWS S3 or Google Cloud Genomics. Which a
team of researchers can then access from their own labs around the world.

~~~
jackcosgrove
Genomic data needs very strong privacy controls. HIPAA would probably prohibit
making entire genomes public without patient consent, even if they have been
de-identified. Just sequencing a fraction of the patient's genome subsequently
could make identifying the entire public genome easy.

~~~
gumberculese
Here are 1000 whole genomes:

[http://www.1000genomes.org/](http://www.1000genomes.org/)

The VCF files are reasonably formatted, the raw sequencing data is in the
FASTQs, which are huge and hard to deal with. Go nuts!

~~~
jackcosgrove
The About page says, "The 1000 Genomes Project developed guidelines on ethical
considerations for investigators doing sampling, outlined in the Informed
Consent Background Document and the Informed Consent Form Template. All
collections included in the Project followed these ethical guidelines and
model informed consent language."

Here is the consent template:
[http://www.1000genomes.org/sites/1000genomes.org/files/docs/...](http://www.1000genomes.org/sites/1000genomes.org/files/docs/Informed%20Consent%20Form%20Template.pdf)

The post I responded to sounded like the genomic data would be uploaded
without consent to a giant public database.

Even with consent the greater concern is that employers, medical providers,
national health services, and health insurance companies could, by sequencing
part of your genome, match it to a public database identifying you and your
entire genome. This could then be used to raise prices, deny health care, or
deny employment.

De-identification is not enough if the material is indicative enough that
efforts to re-identify it can succeed.

Kudos to those advancing science by making their genomes public, but it's a
risk I would not take.

~~~
bduerst
Except it is illegal for employers and insurance companies to do such
discriminatory practices.

With new technology comes new responsibility - we shouldn't shy away from the
tech because we don't want the burden of enforcing regulation.

------
krschultz
I would highly recommend the book 'The Emperor of All Maladies'. When you read
a detailed account of the fight against cancer two things become clear. First,
we had no idea what we were doing for a very long time. Second, the era of
actually fighting some of these more complicated diseases is upon us. We have
been trying to stop cancer for nearly 100 years but only in the last 15-20
have we actually been making any progress. It's a well written book and makes
me quite hopeful for the future.

------
patates
It feels like many of us were so excited about the automation scenarios, we
may have missed what the significance of the latest developments in machine-
learning (both algorithmic and hardware-based) would have in other fields - or
maybe it's just me.

~~~
melling
I disagree but it's a digression. How about we discuss the article?

Update: Please ignore my comment. The original post was changed and my upvotes
have turned to downvotes. Now I can't delete this comment.

~~~
patates
Article starts with discussing how recent improvements in computing led to the
start of the expected discoveries in genetics. I don't understand how my
comment is unrelated?

~~~
melling
You changed your comment. Where is the remark about the singularity? The
entire meaning of your comment has changed.

~~~
patates
I changed "path to singularity" to "automation scenarios" and "IT people and
target audience of HN" to "many of us" to make it more clear. I'm very sorry
if you think it meant something else with those words, I'm not a native
English speaker.

~~~
melling
What are "automation scenarios"? Saying people on HN discuss the singularity
too often vs "automation scenarios" is going from a specific idea to a vague
idea. English is my first language and I would never say "automation
scenarios"

~~~
patates
Programming is mainly about automation and I mean "automation scenarios" as
the general concepts we work on. Improving automation is a path towards
"singularity" (in this case that meaning not AI world domination, but nothing
to do left for humanity as everything is being done automatically) with a nice
feedback loop. Many people here, including me, naturally obsess over the parts
that are directly relevant to our jobs and not think too much about the
possible effect on other industries. Hope it is clear now :)

------
dredmorbius
There's very little meat to support the subhead's assertion.

In Robert Gordon's _The Rise and Fall of American Growth_ , a great deal of
attention is focused profitably on the changes and progress in medicine and
health outcomes from 1870 to present. Most notably, Gordon divides the period
at 1950, noting that life expectencies improves 2x more _before_ 1950 than
afterward (and from my own explorations, far more prior to 1920 than after).

There's been exceedingly little progress in medicine since 1970, at which
point major cancer, heart disease, and virtually all infectuous disease
treatments existed. We've seen many more _treatments_ and more so _imaging and
diagnostic_ capabilities since ... but virtually no changes in outcomes.

Healthcare is a land of very, very, very rapidly diminishing returns, and for
which _shoring up treatment and preventive care for the most under-served_
pays _hugely_ greater dividends than highly invasive or heroic treatments at
the top end. Much of the progress in health outcomes since 1970 appears to be
in minority populations -- that is, the under-served.

Gordon's book was published this year, its information is quite current. I see
little reason to suspect massive improvements in actual outcomes -- impacts
rather than _change_ \-- in the nine months or so since it was put to bed.

~~~
hackuser
This is broadly false; outcomes have in fact improved greatly in very many
fields. Off the top of my head: Far more people surive heart disease and heart
attacks; AIDS didn't even exist in 1970.

~~~
dredmorbius
Gordon's metric generally is QALYs. Yours?

------
savemylife
I hope it brings with it some advances in diagnostics. I have some kind of
autoimmune condition (I think) that has resisted a proper diagnosis for over 2
decades. Whatever it is, I lost my livelihood to it, and now I stand to lose
my savings as well. Since I have no diagnosis I can't even apply for social
security benefits, much less hope to return to work (I used to write code
pretty successfully).

------
astazangasta
It's laughable that they led with the genetic cause for schizophrenia which
(a) probably doesn't exist and (b) wasn't found a few months ago; they found a
weak statistical association across a large number of variants that explains <
3.5% of the variability in disease susceptibility. What this demonstrates is
what we've learned over and over across the past decade with association
studies: yes, we're a product of our genes, and variation affects us, but no,
common diseases are probably not mostly driven by genetics.

For me, the big story in genomics over the past few years is one of massive
failure. We spent a lot of time and effort sequencing tumors in the hopes that
the genetics would tell us something interesting and lead to cures. It did
not. We now have a relatively complete cabinet of the major variants that
drive tumors. Most of these variants we already knew about before we did these
genomics studies (through older sequencing methods from decades prior), and
most of what we learned tells us nothing new.

Genetics is at this point mostly garbage information. Why? Because we don't
know what it means. We still don't understand gene expression, we don't
understand signal transduction, and we can't understand the effects of
mutations without painstaking characterization. All of these things mean our
sudden wealth of knowledge of genetic variation tells us fuck-all about
biology.

~~~
_red
This hysteria exist mainly because most people are led to believes "genes" are
something that they are not.

They are not "blueprints" much less some sort of engineering document.

More realistically, they are a simple list of materials (in this case a
listing of proteins).

They only describe the materials that make up a structure, not _what_ that
structure is nor _how_ it functions.

Its the equivalent of someone saying: 14,234 tons of steel, 23,000 tons of
concrete, 8000 tons of glass...etc. Now, what does it make? Why does it make
it?

~~~
jackcosgrove
So what mechanism carries the information of how the body functions from
generation to generation if not genes?

~~~
toufka
Physics. More specifically, 'conditions'. More specifically, the environment
in which the ingredients are produced determines how the ingredients assemble.
The analogy to the ingredients list is a decent one, but it is also a tad
misleading. You generally do require knowledge of the environment to figure
out how the parts will assemble, but many of the parts _do_ work in many
different environments and can be considered whole and separable objects
rather than ingredients. But trying to separate evolution/life from its
environment is the first mistake a student makes when studying evolution. As a
grandparent stated, if the genes are the starting positions in Conway's Game
of Life, the laws of physics are the rules of the game, and the physical
conditions (temperature, pH, gravity, time, etc.) are the topology and
specifics of the board you'll be playing on. Then you just hit play and
certain concepts self-assemble - the flier, the block, the boat, etc. Some can
then be used as objects in themselves, some can be used structurally, some can
be used to build/destroy structure - that is life.

~~~
jackcosgrove
If the laws of physics are universal (fingers crossed), then this factor gets
canceled out. Obviously organisms which evolved under our physical regime can
only function properly within our physical regime. But this doesn't add any
information as to why one set of genes manifests itself differently than
another set of genes, since the physical laws are the same.

~~~
coldtea
> _If the laws of physics are universal (fingers crossed), then this factor
> gets canceled out_

This is beside the point, as parent already explained what he meant in his
first 2 sentences: "Physics. More specifically, 'conditions'".

So, yes, the laws of physics might be universal, but gravity is X here and N
on the moon, pressure is Y here and M under the sea, temperature, etc...

------
iandanforth
I was under the impression that modern genomics had moved away from the
"gender variants are what matters" mindset. Hasn't greater understanding of
the proteom and the influence of the environment massively complicated this
already daunting task?

------
monknomo
I read that as the "The gnomic era arrives" which seemed pretty reasonable o
me.

------
amelius
I'm still looking for a way to have my genome sequenced (SNP analysis), while
staying anonymous.

~~~
kyberias
While 23andme's terms dictate that you should use your own identity, in
practice you could circumvent that by asking your friend to provide the info
and credit card payment. Preferably same sex.

~~~
adenadel
This is nitpicky, but 23andme doesn't do whole genome sequencing. They use a
genotyping SNP chip that interrogates about 500k individual bases (and imputes
other positions) rather than sequencing the 2x3B base pairs in the whole
genome.

~~~
kyberias
Why do you tell me this? Look what the OP asked.

------
sjg007
I think we are in the genomic platform era.

------
sickbeard
if you don't know if it's real how can you claimed it has arrived?

