Total synthesis of Escherichia coli with a recoded genome

2023-06-19: This list also has a lot of highlights

1. That 40 years ago, “it took 3600 kg of pancreas glands from 23k animals to make 500g of insulin,” enough for 750 people with diabetes annually, but now insulin is made by engineered bacteria.
2. That gene-edited hens “lay eggs from which only female chicks hatch,” which could one day keep 7b male chicks from the macerator each year.
3. That mosquitoes have killed billions of people across human history and still kill 700k people annually, but now we have a malaria vaccine, made by a fungus, that is more than 70% effective.
4. That type A or B blood can be converted to O (universal donor) by using enzymes that chop sugars off cells, and this same technology has been used to convert blood type-A lungs into blood type-O lungs to make “universal donor” organs.
5. That 3k Americans are waiting for a new heart, but xenotransplantation — putting an animal heart into a person — is nearly here thanks to “humanized” pig organs depleted of antigens that cause immune reactions.
6. That 100 years ago, most people with hemophilia died by 13 years of age (at the time, there was no way to store blood, so the only treatment was to transfuse blood from a family member) but now a single injection of a gene therapy, called Hemgenix, can treat people with type B hemophilia.
7. That gene therapies to lower “bad” LDL cholesterol by turning off the PCSK9 gene in the liver could prevent cardiovascular disease for millions of people and have been tested in clinical trials in New Zealand and in monkeys.
8. That multiple myeloma, a white blood cell cancer, has a five-year survival rate of 58%, but a recent clinical trial that treated people with genetically ‘rewired’ immune cells tripled the time it took for cancer to progress, from 4.4 to 13.3 months.
9. That pancreatic stem cells, transplanted into the body, can restore insulin levels and, in some cases, have helped people with diabetes go years without injections.
10. That in vitro fertilization can help people suffering from infertility have children, and same-sex couples may soon be able to do the same by reprogramming their stem cells into eggs.
11. That the COVID vaccines were made in 1 year, partly because scientists mapped the viral genome and shared it online in early January 2020, and the prior vaccine speed record was 4 years, for a mumps vaccine back in the 1960s.
12. That chemical space exceeds 10⁶⁰ molecules, but a screen of 1m molecules still produces drug target “hits,” which means that life (fortunately) exists within a small window of molecular possibilities and drug discovery is not a hopeless endeavor.
13. That microbes on telephone poles and handrails around New York City (and lots of other places) make thiocillin antibiotics that kill normally-resistant bugs, and our present dearth of antibiotics stems from poor economic incentives, rather than a true lack of drug options.
14. That gene-edited microbes can convert industrial emissions from steel factories into acetone and isopropanol in a carbon-negative process and at commercial scales.
15. That all life shares DNA as a language, meaning genes from daffodils and microbes can be inserted into rice to coax the plants into making provitamin A, a molecule that could save the lives of 1000s of malnourished children each year.
16. That crop yields have roughly tripled over the last 60 years and we can theoretically feed 10b people with our current food supply, without chopping down any more forests, which is good because as many trees have been lost in the past 100 years as in the 9000 years prior.
17. That redwood trees scrub enough carbon from the air to offset my breath for 50 years or more, and gene-edited trees that grow up to 50% faster and eat up to 27% more CO₂ than ‘normal’ trees in greenhouses are now being tested in the real world, too.
18. That Rubisco — which is probably, but not definitely, the most common protein on Earth — is slow at stripping CO₂ from the air, but it’s possible to ‘borrow’ protein domains from a turbocharged Rubisco, found in red algae, to boost the enzyme’s photosynthetic rates 2x in tobacco plants.
19. That 150 years ago, we didn’t know that microbes cause disease and now we can view atomic-resolution protein structures on an iPhone.
20. That deep learning models can design proteins that don’t exist in nature, including light-emitting luciferases that are structurally distinct from those found in fireflies.
21. That a green fluorescent jellyfish protein can be fused to other proteins, enabling one to directly observe molecules move through cells, unravel how nerves grow in the brain, or map how cancer spreads through the body.
22. That neurons in the brain or eye can be controlled, with sub-second temporal and sub-millimeter spatial resolutions, using pulses of light or sound, and this has been used to restore sight in people with specific forms of blindness.
23. That digital data can be stored on DNA at a theoretical density of 455 exabytes per gram, which means a coffee mug filled with nucleic acids could store all the data produced in the last 2 years.
24. That cheap DNA sequencing is unearthing ancient human history in the absence of written records, deciphering how our species lived and ate by reading the genetic material found in ancient bones or the counters of Roman fast food restaurants.
25. That DNA editing, gene therapies, and most of the wondrous things in biotechnology are mere adaptations of nature, and there is still plenty of room at the bottom.

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