Comment by dddiaz1 | Hacker News Reader

Comment by dddiaz1 | Hacker News Reader

I have absolutely loved working in genomics. I am a huge believer that genomics will be a huge part of healthcare in the future, and i have two examples to motivate that point that I think may be interesting to the reader.

1) The Moderna vaccine was made with the help of illumina genome sequencing. They were able to sequence the virus and send that sequence of nucleotides over to moderna for them to develop the vaccine - turning a classically biology problem, into a software problem, reducing the need for them to bring the virus in house.

2) Illumina has a cancer screening test called Galleri, that can identify a bunch of cancers from a blood test. It identifies mutated dna released by cancer cells. This is huge, if we can identify cancer before someone even starts to show symptoms, the chances of having a useful treatment dramatically go up.

Disclaimer: I work for illumina, views my own.

I wrote some more about why genomics is cool from a technical point of view here (truly big data, hardware accelerated bioinformatics) : https://dddiaz.com/post/genomics-is-cool/

The thing I'm most excited about long term is biocomputing.

Having Turing complete programmatic control over biological systems has an absolutely endless list of transformative applications.

Imagine being able to program bacteria that can "infect" the patient and attack tumor cells, or act as fodder to keep autoimmune disease in check.

Or let's say we could program stem cells into "liver repair mode" to go and differentiate into new liver cells.

Then the implications for things like drug synthesis with the ability to programmatically control enzyme levels to compile more or less arbitrary biosynthetic pathways into fast growing photosynthetic algea, turning CO2, water and sunlight into medicine.

It's still a long way off being at that level of applicability, but man oh man it's gonna change everything.

Sounds great until natural selection kicks in, and because DNA replication is largely a lossy process, suddenly the thing you programmed the organism to do mutates to do something else a whole lot more problematic.

Imagine a software heisenbug, but instead it's a life form that you can't kill -9.

The idea of tailor-made medicines in a vat is awesome, but as far as creating a bacteria to "specially target" certain cells seems like a disaster waiting to happen.

Those are certainly real problems, and I'm not a cell biologist, but I'm not convinced these problems are insurmountable.

For instance, it might be possible to use ECC to get around transcription errors. It could also perhaps be ensured that any rogue "clinical biocomputer" could be easily treated with antibiotics or specifically engineered bacteriophage virus.

Like I said, the technology is very far off from having real world applications like this. At the moment it feels like we're in the analogue of the 40s and 50s for conventional computing. The field is still just inventing the very basic building blocks. It's going to be very limited in use, wildly dangerous(look up mercury delay lines) and unreliable for decades to come.

Polymerase without error correct has error rate of 10**-6. With error correct it's 10**-9 to 10**-12.

Considering the current treatment in the worst cases(where more targeted treatments don't exist) is to blast the pasient with radiation and poison(chemotherapy) and hope it doesn't kill them, I'll take those odds.

Except a rogue bacteria won't just kill you, it could escape beyond you and kill millions.

Chemo/radiation only kills the patients it was given to ( not entirely true - if the treatment caused mutations in the germline and the patient subsequently had children, the effects of the treatment might be passed on - but still very limited ).

Bacterial infections are generally very treatable though. Even when the bacteria aren't engineered. And especially when they are, because why would you leave any antibiotic resistance in an engineered bacterium?

Bacteria are the scariest when they've had the time to develop resistance to multiple different antibiotics.

Additionally, a bacterium that's engineered to be almost completely harmless evolving into a deadly strain in vivo is fairy unlikely in itself, especially if transcriptional errors can be reduced several orders of magnitude like GGP suggested.

Adding to that the option of hospitalisation or even home isolation to reduce risk of transmission, the risk of this resulting in some huge lethal epidemic must be pretty miniscule.

It's hubris to think we are at a stage where human scientists are so disciplined and knowledgable that we can start patching existing life-forms in such a safe enough way so as to target certain types of cells reliably over time and not others.

Software is essentially a cleanroom in the sense that the environment tends to be deterministic and man-made, and that is still riddled with unexpected accidents. Fortunately we can turn it off, fix the bug, and redeploy and the people involved in that tend to survive.

> Additionally, a bacterium that's engineered to be almost completely harmless evolving into a deadly strain in vivo is fairy unlikely in itself, especially if transcriptional errors can be reduced several orders of magnitude like GGP suggested.

The proposition was to engineer a bacteria that targets and infects a particular type of human cell to kill it. Creating medicines in a vat (like insulin) is different from releasing infectious agents in the wild. I was under the impression that this was obvious, but apparently not.

>It's hubris to think we are at a stage where human scientists are so disciplined and knowledgable that we can start patching existing life-forms in such a safe enough way so as to target certain types of cells reliably over time and not others.

I never said we're at this stage now or even close to it, in fact I explicitly said the opposite:

>>>>Like I said, the technology is very far off from having real world applications like this. At the moment it feels like we're in the analogue of the 40s and 50s for conventional computing. The field is still just inventing the very basic building blocks. It's going to be very limited in use, wildly dangerous(look up mercury delay lines) and unreliable for decades to come

As for comparing creating medicines in a vat to using bacteria as an active treatment, you're the only one making that comparison. The paragraph you responded to wasn't about in vitro drug synthesis at all, so I'm not sure what your point is here. Yes, it's obviously different. I never said otherwise. It's perfectly possible to target bacteria to specific tissues; wild bacteria already do this.

My point was that a bacteria engineered to target a malignant tumour, to be very treatable with antibiotics or bacteriophage, and to have a strongly reduced rate of mutation, is extremely unlikely to evolve into a pandemic, and is likely to be much safer than chemotherapy and radiation.

> My point was that a bacteria engineered to target a malignant tumour, to be very treatable with antibiotics or bacteriophage, and to have a strongly reduced rate of mutation, is extremely unlikely to evolve into a pandemic, and is likely to be much safer than chemotherapy and radiation.

Did you know bacteria have horizontal gene transfer? ie antibiotic resistance isn't just evolved and passed to children ( vertical ), it can be passed to peers horizontally.

It also happens outside bacteria - but bacteria have active mechanisms to enable this - that's how antibiotic resistance spreads - not just from parent to child, but peer to peer like a meme :-).

Safety is a complex topic, and you'd need to consider on a case by case basis - PhD students engineer bacteria every day ( something that had a self imposed ban in the 1970's I think ) - however that's within the context of standard platforms and each and every one should have a risk assessment.

Don't get me wrong, I think it could be done, but there is a Genie and a bottle here and it's best to think twice.

I'd like to see both a kill switch ( beyond antibiotics ) and some sort of growth external dependency - ie they need something you provide to survive as well.

Purposefully blocked for certain countries?

"The Amazon CloudFront distribution is configured to block access from your country."

what kind of math/cs/algorithmic skills do you think one should work on to get a job in this kind of company ?

There are two main flavors of jobs. For one you’ll want to be a phd in something like physics or math. For the other Amy standard software engineering background will do.

TBH I'm surprised how hard Illumina is already pushing Galleri as a product. Current ctDNA/cfDNA are imperfect for advanced cancers which should have a lot of shedding to begin with. Additionally CHIP is and outstanding issue. DNA methylation sequencing has promise but I feel more data would be needed to truly make diagnostic findings. So to see Illumina market it as a ready to go product is quite worrying. It may burn a lot of people

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