As Feynman said nearly 60 years ago:
> We have friends in other fields – in biology, for instance. We physicists often look at them and say, "You know the reason you fellows are making so little progress?" (Actually I don't know any field where they are making more rapid progress than they are in biology today.) "You should use more mathematics, like we do." They could answer us – but they're polite, so I'll answer for them: "What you should do in order for us to make more rapid progress is to make the electron microscope 100 times better." https://www.zyvex.com/nanotech/feynman.html
Turns out that biologists (and chemists and some physicists working on bio) ended up hacking together a bunch of techniques that work far far better than wildest dreams of current microscopy. It requires tons of informatics afterwards, but it gets answers and information of such magnificent scale that even an electron microscope 100x better couldn't dream of.
It turns out you don't just need the resolution, you also need a massive field of view, and a massive volume of field of view not just a plane, to get close to the discoveries that go into a state of the art paper these days. I'm not sure if microscopy can catch up, it if it ever does it will be through massive deep learning on teravoxels or maybe a few orders of magnitude more. That's not in the cards anytime soon, as far as I know.
The ability to see the actual atomic organization of a molecule (and its various confirmations) of previously "uncrystalizable" compounds is also amazing. There is money to made building these lab systems! It needs to be automated ,but everyone will need to upgrade.
Progress in sequencing is also exciting, but don't discount microscopy!
The field of connectomics is also exciting in this regard.
However, I'm more hopeful for future versions of microscopes which are not even in the realm of imagination of current researchers (an MRI microscope with micron resolution? Yes please!)
I do wonder how easy/costly it is to compare differences in single cells via sequencing. I realize there are methods for cell isolation using stuff like microfluidics. But a lot of these methods use elements of microscopy.
My sense has always been that next-gen sequencing coupled with superres microscopy is the way forward.
> One of my biggest personal fears is working in the wrong field to achieve the goal I care about.
Other things that come to mind:
- Size of cells
- Texture / shape of cells
- Local microenvironment
- Morphology of tissue
Combining both seems like a promising step forward (as commenters here have already mentioned).
This struck me as a strange analogy, considering DNA's inherent fragility, but it would make more sense compared to modern software than hardware.
Alternatively, it also makes sense if "hardware" means a particular model/architecture, with DNA corresponding to an HDL, rather than an instance of hardware (e.g. single CPU, server, or smartphone). A frequent enough topic on HN is the challenge archivists have with archaic software and data formats, even if all the original collections-of-bits are faithfully preserved.
DNA in living cells has some fragility because it is in an aqueous solution and also actively used to generate RNA. DNA out side of cells is even more fragile, it will inevitably be eaten by bacteria. But put DNA in the right sterile environment, it can last for thousands of years and has great resistance to electromagnetic interference.
This has echos of No True Scotsman. Computer storage media also have ideal conditions that can be used to extend their lifetimes (though, granted, not indefinitely, AFAIK).
What about in real conditions, subject to things like temperature variations (including "extreme" heat that non-operating computer hardware can do just fine in), exposure to light, humidity from the air (to put it back into aqueous solution occasionally), and common oxiders found floating around in the air?
Could one rely on an arbitrary single strand to last even 5 years in an office environment, or are numerous, RAID1-style, copies required to maintain fidelity?