$100 Human Genomes!!! Please Remain Calm, Limit of 1 per Customer

[J11]

The exponential decline in the cost to sequence a human genome has stalled out over the last ~5 years.
Basically, we hit a price point in which long line ups should have formed online and elsewhere to be sequenced;
surprisingly this never happened.

It is not hard to imagine that the commercial strategy was to maximize profit by holding the price at $1,000.
A certain corporation has a near monopoly, how doesn't this mean a large pay day?
$1,000 does seem reasonable for ~ 100 Gigabases, it did of course cost about $1 billion for the first genome.

However, what we have seen is a fairly minimal market emerge for full genome sequencing.
Even with monopoly pricing power, there is no guarantee that people will actually buy the product.
One does not like to cast aspersions, though some people might be a little bit too careful (i.e., cheap).

Cost Genome.png

OK, time for a Dutch auction.
What happens with a price point of $100 for genome sequencing?
Perhaps somewhat unsightly wrestling matches as shoppers try to buy the limited number of door crasher specials?
Please everyone decorum!

One might also speculate that at such a price point there could be profound implications for cancer treatment.
If you could sequence circulating tumor cells for only $100, then you could identify optimized therapy to target
patient specific pathways that are malfunctioning. With such power, it is not unreasonable to expect that you
might go from treatments with ~30-50% efficacy to 100%.

This is extremely exciting!
A $100 genome is too low a price not to load up the buggy. (Remember the run on toilet paper; like that)
It would be helpful though before the buying frenzy to use our buying power to make sure that customers receive
a high quality product. I have found with genomics products that without market pressure even basic features can be absent.
For instance, my last exome sequence did not have rsnumbers or other metadata for the SNPs. This is almost an
essential feature. Yet, if people go to the bargain bin they might not realize how important this feature is; until after they spent
their money and have lost their buying power. It would cost virtually $0 for the sequencers to include the information, though surprisingly this apparently is not enough motivation. Getting these basics down beforehand will allow for a smoother rollout of mass sequencing.

https://www.freethink.com/articles/genome-sequencing

I am unable to locate the reference from the ICAD website at this moment (did they remove it?), though if I recall
correctly, there was an announcement that a conference would be held in September (NIH? Alzheimer Association?)
to talk about next generation sequencing in AD. That would seem like a very wise idea, considering that an
ocean of sequencing data is on the way.

How will we cope with all of this sequencing data? 100 million full genomes x 100 Gigabases? Do we really have computers
that big? This amount of sequencing should help to rapidly decode the dementia genome.

I have struggled away to the best of my ability for a few years trying to find our AD variant. With the truly
massive scale of genomic sequencing approaching this lack of success likely will not continue. Some anonymous
online url that offered to GWAS uploaders genomes to find AD variants could be a highly cost effective way to unlock
the AD genome. If you take away the cost of the sequencing (let the people pay for the sequencing), then whatever
cost that remained would be minimal. Even $100K to run the software seems excessive. GWAS sequencing for the people.


The current AD sequencing efforts have been fairly disappointing:

"Alzheimer’s Disease Sequencing Project (ADSP), making for a total of 25,982 samples ...
the dataset included exome sequences from 12,625 AD cases and 8,693 controls "
https://www.alzforum.org/news/conferenc ... mers-genes

While the 500K UKBB identified ~30K AD proxies, though ingeniously imagined, it was still below the scale that we need.
We need 1 million , 2 million AD genomes. The genetics of AD would then be totally revealed.

Perhaps if necessary the APOE4 forum could serve as a front end for such uploads (if no one could
recognize the profound importance such an unlock would represent). Not totally sure, though, who would have a big
enough cloud.

What is particularly exhilarating is that we are now possibly only months away from actually witnessing the unlocking
of the human genome that we have waited so many decades to occur. This is a profoundly important moment for our species.
The emergence of new species of humans is imminent.

[circular]

We need 1 million , 2 million AD genomes. The genetics of AD would then be totally revealed.

Bingo! ... plus how many non-AD controls, and how to certify the patient had AD and wasn't one of the roughly 1/3 who are misdiagnosed with it?

Perhaps if necessary the APOE4 forum could serve as a front end for such uploads (if no one could
recognize the profound importance such an unlock would represent). Not totally sure, though, who would have a big
enough cloud.

Besides the cloud/server space, the privacy requirements are staggering and must come with a heavy price tag. It's one breach after another these days.

The emergence of new species of humans is imminent.

Sooner the better, but how can we control which homo sapien genes are preserved in the new species after they interbreed the way our ancient ancestors did with Neanderthals and Denisovians?! It will be love at first sight (or worse) vs. evolution over thousands of years to sort that out.

Sorry I seem to be a 'Debbie downer' today. Keep the faith

[floramaria]

What is particularly exhilarating is that we are now possibly only months away from actually witnessing the unlocking
of the human genome that we have waited so many decades to occur. This is a profoundly important moment for our species.
The emergence of new species of humans is imminent.

This is where we are different, J11. You find this exhilarating: I find it frightening. My fear is mainly based on who will control the technology and to what purpose. You must have a generally sunnier view than I do of humans as we currently exist to believe this will turn out "well"... whatever that means.

[J11]

Flora, yes I agree this is quite scary.

I think it is one of those times where the best thing to do is to raise your hands in the air and wait for the roller coaster to go straight down and pretend that everything is fine. I suspect that those with any understanding of this could not possibly be so nonchalant; Just hand it over to adult supervision.

Human society has a certain social logic that has evolved through thousands of years. Even dementing illness fits into this logic; I tend to agree with others on forum that curing AD will have counter-intuitive effects. I have seen the problems that occur in people's lives when they do not have caregiving roles to fulfill: The so called winner's curse. One of the medical workers told me how blessed I was to be in a dementia family, I did not fully understand what was meant by this at the time (I think at the time I would have taken the other side of the argument), though with some time and perspective I now tend to feel that it did exert a positive in my life. It certainly reframes the way I comprehend what is important in my life and how I view what others value.

Yet, with the potential to genetically reengineer everything, an entirely new social logic will emerge. It probably will take a bit of time to get our bearings when the social disruption occurs; at least it'll fun be for the kids. A world saturated with ever increasing intelligence will be very exciting. 1,000 IQ enhancement, can't wait!

Exciting and highly disruptive. We clearly know that fully unlocking the genome (as is now on the immediate time horizon) will have extremely dramatic effects. The big idea here is that extreme polygenics implies extreme phenotypes. With millions of genotypes available full unlocking of human intelligence, AD, human psychological traits etc. could occur rapidly. Human intelligence is going to launch. What has happened to artificial intelligence over the last 50 years will happen to us. Increasing IQ by 3-5 points might not seem like much until all of sudden it's 100 or more points. Yet, even fairly minimal changes in human intelligence in the past have dramatically changed human behavior.

[J11]

circ, this is so over the top. As soon as the sequencing kicks into gear, things will quickly become quite interesting.

The first obvious response will be a complete fertility collapse.
While this might now already be underway, supporting evidence has yet to be reported.
Typically people will only respond after the exponential wave of technology has crashed unto shore and we are
knee high in water. With population scale full genome sequencing, such response could happen sooner or it could happen later,
though either way it seems inevitable.

If we truly are right on the edge of unlocking the human genome, then this could unfold much more rapidly than might be commonly expected. As soon as there are a few million human genomes sequenced we know that this will be enough to open Pandora's box. Typically with exponential curves nothing ever seems to happen until the moment just before you are completely swamped. Parents to be who want to make the rational choice would probably favor waiting until such unlock occurs and there is greater clarification about how this knowledge might be applied in genetic engineering.

Some of the number crunching associated with this still is in flux. Yet clearly as a parent you do not want to be highly uncertain
whether the approaching generation that will compete in the job market with their children will have a 3 point or 20 point IQ advantage. 3 points are already on the table; that is with merely using selection. A 20 point disadvantage would meant that there children would be functionally unemployed throughout their working lives.

The objections that you mentioned would not seem to be strong obstacles given the current technology.
For instance, the question of identifying those with "true" AD probably will not be a major concern.
With the UKBB, they simply asked who had a parent with AD and used these "AD by proxies" as equivalent to AD.
With a large enough sample, all you need to do is enrich the sample with signal even when there might be
a fair amount of noise; The control group would be everyone else. When you remove the epsilon 4s,
mostly everyone else is part of the control. Given that most people do not have high AD risk, finding controls
will not be a challenge.

In terms of privacy, I am not really sure how realistic it is to think about absolute genetic privacy anymore.
So much of our shared DNA is now floating around in all sorts of supercomputers. While we can decide about
our own wishes with our own DNA, others who also share fragments of our DNA have their own wishes about how
they want to protect their genetic privacy.


Hmm, yes breeding. That certainly could be a problem. I am unsure whether with their super-duper enhanced IQ
they might find time in their schedules for such activities. Perhaps the job of the unenhanced (i.e., us) will be to run
the incubators, so that the new human species can remain demographically viable.