Tag: biotech

Flu, HIV, Nipah vaccines

Even as we have shown that our mRNA-based vaccine can prevent COVID-19, this has encouraged us to pursue more-ambitious development programs within our prophylactic vaccines modality. Today we are announcing 3 new vaccine programs addressing seasonal flu, HIV and the Nipah virus, some of which have eluded traditional vaccine efforts, and all of which we believe can be addressed with our mRNA technology. Beyond vaccines, we are extending our mRNA development work to a total of 24 programs across 5 therapeutic areas

Health Trends

For too long, we’ve confused the status quo for stasis in healthcare. We’ve accepted certain things as true, things we believed to be immutable, intractable, or at the very least, extremely hard to change—like that it takes years to develop a vaccine, or that virtual medicine will never scale for doctors or patients, or that the regulatory system can’t adapt to innovation quickly enough to support lasting change. But then came 2020.

  1. Patient data moves beyond the EHR.
  2. Health insurance gets unbundled.
  3. Virtual care becomes a first-class citizen…
  4. …with its own operating system.
  5. The home becomes a primary site of care (again).
  6. Mental health gets engineered.
  7. Value-based care comes for Rx.
  8. Illumina for X.
  9. Infectious diseases attract investment again.
  10. Clinical trials (finally) go digital
  11. Personal genomics finally goes clinical.
  12. Working on rare diseases gets more common.
  13. Biotech reaches the industrial age.
  14. Targeted delivery of complex therapies.
  15. Biotech R&D goes more virtual.
  16. The bright line between life sciences and care delivery blurs.

2020s Technology

Therapeutic plasma exchange is FDA-approved (not for aging, but for a bunch of other conditions). I imagine there remain prohibitions on advertising that it can add years to your life, but it is safe, and a doctor can prescribe it off label. It’s also cheap. An automated plasmapheresis machine—which lets you do treatment after treatment—can be bought online for under $3000. That is less than the cost of a single transfusion of young blood sold by the startup Ambrosia. How long until someone opens a clinic offering plasma dilution? I bet someone tries it in 2021. If it works, people will get over the weirdness, and it could be commonplace by 2030.

What is more plausible this decade is enhanced and advanced geothermal systems. The legacy geothermal industry is sleepy, tapping energy at traditional volcanic hydrothermal hotspots—forget about it. The next generation of the industry, however, is a bunch of scrappy startups manned by folks leaving the oil and gas industry. The startups I have spoken to think with today’s technology they can crack 3.5¢/kWh without being confined to volcanic regions. With relatively minor advancements in drilling technology compared to what we’ve seen over the last decade, advanced geothermal could reach 2¢/kWh and become scale to become viable just about anywhere on the planet. Collectively, the startups are talking about figures like 100s of gigawatts of generation by 2030. I’m watching this space closely; the Heat Beat blog is a great way to stay in the loop. As I wrote last month, permitting reform will be important.

The 2020s will be a big decade for sustainable alternative fuels (SAF). Commercial aviation can’t electrify—batteries will never match fossil fuels’ energy density. Given political realities, aviation has no choice to decarbonize, which means either hydrogen fuel or SAF. Hydrogen fuel is much better than batteries, but still not as energy dense as fossil fuels or SAF, and so my money is on SAF, and particularly on fuel made from CO₂ pulled from the atmosphere. It is easy to convert atmospheric CO₂ to ethanol in solution; and it is easy to upgrade ethanol into other fuels. But it is hard to separate ethanol from water without using a lot of energy—unless you have an advanced membrane as Prometheus Fuels does. I have written about Prometheus before and continue to follow them closely. Their technology could decarbonize aviation very suddenly.

Construction tech is another area to watch. Whether it’s 3d-printed homes as imagined by Icon, or advanced manufactured housing as designed by Cover or Modal, there has to be a better way to build than our current stick-built paradigm. Housing costs have skyrocketed largely due to zoning rules, but construction technology is another lever by which we can increase housing productivity. This is another area where the barriers don’t seem to be primarily technological.

Continuous blood tests

“A blood test is great, but it can’t tell you, for example, whether insulin or glucose levels are increasing or decreasing in a patient” The Real-time ELISA is essentially an entire lab within a chip with tiny pipes and valves no wider than a human hair. An intravenous needle directs blood from the patient into the device’s tiny circuits where ELISA is performed over and over.

Metagenomic testing

Scientists have developed a single clinical laboratory test capable of zeroing in on the microbial miscreant afflicting a patient in as little as 6 hours – irrespective of what body fluid is sampled, the type or species of infectious agent, or whether physicians start out with any clue as to what the culprit may be.

The test will be a lifesaver, speeding appropriate drug treatment for the seriously ill, and should transform the way infectious diseases are diagnosed. Conventional diagnostic tests are designed to detect only 1 or sometimes a small panel of potential pathogens. In contrast, the new protocol employs powerful “next-generation” DNA-sequencing technology to account for all DNA in a sample, which may be from any species – human, bacterial, viral, parasitic, or fungal. Clinicians do not need to have a suspect in mind. To identify a match, the new test relies on specially developed analytical software to compare DNA sequences in the sample to massive genomic databases covering all known pathogens.

Medicinal chemists uplevel

Are medicinal chemists taking it too easy?

In medicinal chemistry, we have now reached a state where millions of building blocks have previously been engineered and can now be used in molecular design and synthesis. In addition to the increase in the number of new amines, boronic acids have been another fast-expanding reagent class since the introduction of the Suzuki coupling method. And if we can get our work done via such easy reactions – plenty of experience in doing the reactions, relatively easy purifications, existing scaleup expertise, and so on – then why shouldn’t we?

2010–2020 synthetic biology

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.

Designer Proteins

the baker lab / rosetta are still going strong, with complementary ML approaches:

The hope is that the next time there’s an outbreak, within 2 days, we’ll have models of candidates

2023-07-13: Protein design is getting real.

10–20% of RFdiffusion’s designs bind to their intended target strongly enough to be useful, compared with less than 1% for earlier, pre-AI methods.Biochemist Matthias Gloegl has been hitting success rates approaching 50%, which means it can take just a week or 2 to come up with working designs, as opposed to months. “It’s really insane”. The latest protein-design tools have proved to be extremely powerful at creating proteins that can do a particular task — so long as that function can be described in terms of a shape, such as the surface of a protein to bind to. Tools such as RFdiffusion aren’t yet able to handle other kinds of specifications, such as making a protein that can carry out a particular reaction regardless of its shape — when “you know what you want but you don’t know what the geometry is”.