Blockchain Technology & Human Genetics

in science •  2 years ago

It is inarguable that we've recently undergone a "Greater than Moore's law" advancement in sequencing our genome. 16 years ago, sequencing an entire genome would have taken 16 years and cost $3 Billion dollars. Now you can do it at home for a cost of $1,000 and it will take about a week.

Logically, this will become a simple sensor on a device like a smartphone and it will sequence your entire genome in a few seconds. That's perhaps 5 years out at the earliest, right?

Yes...
Except that it's not 5 years out anymore, it's here right now...

You can know your entire genome, and it is already small enough to fit in the free space on your cellphone or laptop.

You can get that down even further. If you simply take the deltas (differences) between you and the "reference genome". The maximum size of the delta set for a viable human is 1.4MBs. This is small enough to fit on a floppy disk. Or, a blockchain?

But what is this "reference genome?" Where did it come from?

The genome published by the HGP does not represent the sequence of every individual's genome. It is the combined mosaic of a small number of anonymous donors, all of European origin. The HGP genome is a scaffold for future work in identifying differences among individuals. Subsequent projects sequenced the genomes of multiple distinct ethnic groups, though as of today there is still only one "reference genome."

A small number of anonymous donors? All of European origin? Why?

It's an artifact of the selection process. The work was carried out in areas that were predominately European. No Nazis or Illuminati conspiracies were involved, despite the humor I was trying to convey in my last blog topic.

The fact is, these are just normal people like you and me. They are very smart and dedicated to what they do.

Still who were these donors?

In the IHGSC international public-sector Human Genome Project (HGP), researchers collected blood (female) or sperm (male) samples from a large number of donors. Only a few of many collected samples were processed as DNA resources. Thus the donor identities were protected so neither donors nor scientists could know whose DNA was sequenced. DNA clones from many different libraries were used in the overall project, with most of those libraries being created by Pieter J. de Jong's lab. Much of the sequence (>70%) of the reference genome produced by the public HGP came from a single anonymous male donor from Buffalo, New York (code name RP11).

We know that 70% of the reference genome came from a single person who is anonymous, but I'm wiling to bet it's this guy...

Pieter DeJong
If you're singlehandedly responsible for sequencing 70% of the reference genome, at a time when the failure rate was enormous, you'll probably need more than a single sample.

So this is telling us that >70% of the "reference genome" came from what the future may well describe as a "genetic adam". There is a precedent in nature for it. About 10,000 - 75,000 years ago, the population was "bottle-necked" for some reason.

Why Adam/Eve or possibly Noah?
It's because Religions aren't just stories someone made up!
They are scars imprinted on all of the descendants of a rag tag band of survivors of something catastrophic. This is why these stories fascinate us endlessly and I'm willing to bet it's our spirituality that allowed us to whether that without going completely insane.

What the hell happened? We just don't know. These stories predate our known history and all we have are artifacts. Scars embedded in our language, our religions and our genome. This survival came at the cost of our genetic diversity.

You can take any 2 humans on earth and their genetic differences would fit on a floppy disk. But you can take any two puppies, born any where in the world, and their differences would require a stack of floppies two feet high.

So besides the one guy we know about, who are these other "reference people" that we have already backed up?

DNA from five different individuals were used for sequencing. The lead scientist of Celera Genomics at that time, Craig Venter, later acknowledged (in a public letter to the journal Science) that his DNA was one of 21 samples in the pool, five of which were selected for use.

Alright so Craig Venter is obviously one.

Who else?

In 2007, a team led by Jonathan Rothberg published James Watson's entire genome, unveiling the six-billion-nucleotide genome of a single individual for the first time.

So James Watson is another.

Note that James Watson recieved the Nobel Prize for figuring out what DNA looked like.

These are the 2 people we know for sure and one other guy that we can be 70% certain about.

The bulk of the reference genome is actually chimera/mosaic composed of 5 people. All of whom are documented to be European descended, three of which are males.

If we needed to "restore our humanity", from this reference genome.

We're all going to end up with blond hair and blue eyes.

But why would we need to "reboot" our species? Isn't that a bit extreme?

Yes, it's extreme and that's the point. You don't take a backup of your data because you know your hard drive is going to fail tomorrow. You keep regular backups in case the unforeseen happens.

The fact is, the Human Genome Project to sequence the genome, was a "moon shot".

Just like going to the moon triggered enormous advancements in information technology. The Human Genome Project 1.0 was a "moon shot", that resulted in a "Greater than Moore's law" increase in knowledge about our genome as well as advances in the technology to sequence it.

Now we're about to undertake Human Genome moonshot 2.0

The Human Genome Project - Write (also known as Human Genome Project-Write, Genome Project-Write and HGP-Write), formally announced on 2 June 2016, is a ten year extension of the Human Genome Project, to synthesize the human genome. The human genome consists of three billion DNA nucleotides, which have been described in the Human Genome Project - Read program, completed in 2003. The newly created HGP-Write project will be managed by the Center of Excellence for Engineering Biology, a new nonprofit organization. The researchers expect that the ability to synthesize large portions of the human genome would result in many scientific and medical advances.

Genetic engineering has already reached the stage where anyone can do it at home. There are actually kits you can purchase in order to modify model organisms in novel ways. These kits have very detailed instructions because...

They're intended for Junior High students!

The "hello world" of genetic engineering is to get bacteria to glow in the dark.

What happens if you accidentally replace your own microbiome with this glow in the dark, ampicillin resistant e. coli? That's not the future, it is something actually happening right now.

Yet now we're about to moonshot the ability to synthesize our own genome, not just the genome of model organisms. But the fact is, we don't really know our own genome. If we make a mistake and end up having to "fix it", by restoring from a backup, we're all going to be using someone else's backup.

Herein lies the problem. Despite having what amounts to a "core dump", of our genome. We still don't know what the bulk of this code does and there is currently no debugger to step through it. We're going to have to reverse engineer it and that's what we're doing now.

The moonshot 3.0 we've just embarked upon will change all of that. There has never been a more exciting or interesting time to be alive. We'll get a genomic debugger and editor out of this and probably a compiler and runtime simulator as well. The truth is we've already sorted out most of the "update" mechanism, and that will only get easier as nanotech and genetics begin to merge.

We already have the editors and we already have tools to update living organisms with new code.


We just don't really know what we're looking at yet, when we stare at that code. Because mother nature is the ultimate hacker and she didn't leave any comments.

The logical extension of this is that eventually we will be able to control our own genome directly. We just need to figure out what this machinery and it's programming are actually doing. The logical net result is that we will have the ability to write "genetic algorithms and apps", to modify our own bodies directly.

You can bet we're going to be sharing these one way or the other.
Because we already do this "sharing of new code", every year when we spread the cold or flu around.

I am not afraid of the technology. However I am concerned with the consequences.

If we edit out traits that we consider negative, such as eventually turning into a fat old bald guy. What happens when the same selective pressures that caused the bottleneck, repeat again?

The solution here, is not to demonize the technology. The solution is to provide an adequate backup solution in order to save the "missing information". This should allow us to restore our individual genetic information back to the original programming that nature spent a few billion years hand optimizing to run on our unique bits of molecular machinery. Unique bits which are not included in the reference genome at all.

We should do this, not only in case we make a colossal mistake, but also in case we make a relatively minor mistake.

How would it be, to download a simple "burn fat +10%" app to our body. Only to find out years later that as a side effect, our bodies are constantly flooded with sugar, thereby turning our blood into syrup. Forcing our pancreas into a "hyper stressed" mode eventually shutting it down and making you an insulin dependent diabetic, with no possibility of a "code roll back".

Also, there's the good side of this. Someone who is a Type 1 diabetic could just download a cure from someone genetically similar with no diabetes. If it doesn't work or turns out to have nasty side effects, they can just roll it back.

So here is what I would like to accomplish.

I propose building a blockchain backed "life bank", that allows us to upload our own genomic information and place it under lock and key so that it can be read on demand if needed, but cannot be overwritten. Something we can append to, as more information about our own internal diversity becomes available. The primary purpose would of course be to protect against existential threats. But also just the occasional "whoops!". All without worrying about suddenly waking up as a 6'2" 180lbs Nordic man with blond hair and blue eyes, because we had to restore from someone else's backup.

Some final thoughts from the inventor of CRISPR/Cas9, you should hear her out too.

I am not afraid of the technology. However I am concerned with the consequences.
The next step will be our connectome.
Oh wait, we have that too.
Perhaps, we should consider taking a backup of that as well.
I'll explain more on how to do that in my next blog, if this topic generates sufficient interest.

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Good thing you did another post on genetics.
I think yesterdays post just went over most peoples heads.

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@echoesinthemind
Yes. That's true. Yesterday's post was more focused on trying to get the handful of people who are concerned about conspiracies and what not, to think about these issues instead.

There was quite a bit of facetious sarcasm especially in the opening lines. But I was trying to draw the attention of people who might think that sort of conspiracy stuff is real. The reason is that those types of fantasy fear ideations are the result of a brilliant mind that is bored and seeking connections which are not there.

By drawing their attention to something that could be a real problem, I was hoping to give their minds something else to think about. Problem is I laid it on too thick and my message got lost in the noise.

So this is intended as a counter to that.

Hopefully I managed to send the right message this time which is...
We're already a lot further along than most people suspect. Huge amounts of money have been committed to a moon shot 3.0 and the net result will be a whole new understanding of our genome and what it's capable of doing. Inquiring minds should want to know.

This is mindblowing. And you hardly ever hear that from me, please trust me on that one!
I´m not sure that I´m not terrified by this,but I also do see the possibilities,and they are mindblowingly exciting. If we can avoid some unfixable "bugs" that would wipe out humanity. Emphasis on unfixable,most "bugs" would be fixable.
But I would like to know more about the theoretical possibilities and limitations of this technology. Do you have some good sources to recommend?

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@kooshikoo
The very best resources I have at the moment are linked in the article. If I track down better resources I will. Oddly enough I found the minion sequencer after posting my first article. So their site is probably the most current out there at the moment.

I also highly recommend Carolina Biologicals in general. They have excellent science kits for kids and adults.

I'm all about backups to the genome, but it frustrates me that you cant patent your own DNA, only someone else's. This means that big pharma and the medical industry can profit greatly off of "Designer Genes" that they literally just stole from patients. I like your solution, a sort of "copyright" on your own code.

Bring on the cat-ears and eagle eyes! CRISPR excites me to no end.

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@quanatumanomaly
Well if Wikipedia can be trusted, it looks like you can't patent anything found in nature. This includes a human genome, yours or anyone else's. You can only patent particular methods and therapies. For example, you can cure some forms of cancer using CRISPR and herpes and some snippets of normal DNA.

However that's not even in human trials yet. But I read they are trying it out on something closer to humans than lab rats now.

Fact is, some viruses would make the perfect framework for nanobots if we can make sure to include a way to deactivate them if they exit the body of the host they were created for. Just imagine the nightmare that would ensue if we had "nano enhanced" parasites such as mosquitoes or lice, because our cure for cancer decided to make a species jump.

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Oh wow that's a fairly recent change (2013 ruling). It was a bit different in the late 90's when I was following the research much more closely (and the first time I did my one electrophoresis), so good to know.

Wow, this was such a thought-provoking and enjoyable read. Thank you for taking the time to compile this information and your perspective on the implications into one post. We really are living in incredible times... I can't wait to see what genomics will look like in another 20 years.

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@runaway-psyche
Thank you! I really appreciate the compliments.
Evidently there is an old chinese blessing/curse which reads...
"May you live in interesting times."
I think right now is probably the most interesting time in history, we've effectively come full circle. What used to take hundreds of researchers and billions of dollars in lab equipment can be done at home by one person for less than a week's salary.
I'm excited to see how this plays out on the synthesis end now too.

you're spot on with the article. but there's an error in the wikipedia quotation: the human genome is 3 billion pairs of nucleotides, that is 6 billion nucleotides, not 3. anyway, all cool.

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@cristi
Yeah I didn't fact check Wikipedia on that. What I do have that I know for a fact, is that the total human genome deduped but uncompressed is 1.3GB. However once you examine the deltas between any two people that number drops to 1.4MB.

Good catch and I'm going to let someone who actually works with this stuff for a living update the Wikipedia article.

Thanks for the compliments!

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keep posting these great articles!

I don't need a whole new body, how about creating a new pancreas and immune system? (I'm a type 1 diabetic, the victim of my own body's attack on itself.)

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Yeah so it was only 4 lines or so, but you were covered there.
Also I never said anything about actually getting a new body. Just changing significant attributes.
All of this would be about treating your genome as your own personal app store.