Everything is Cabbage. Now It's Gene-Edited.
Plus: The F.D.A. makes an unexpected decision.
I live in Cambridge. It’s a town that has that quaint-suburb-that-is-still-just-as-expensive-as-the-big-city feel. My apartment is old and kinda spooky, with creaky floorboards and weird nails in the ceiling that I don’t fully understand. The neighbors are great, too. Yesterday, I saw a nice woman sitting outside with her bird while a man, just a bit down the street, donned his boxing gloves and went to battle with a telephone pole.
In this issue: CRISPR’d food is gonna hit U.S. shelves, it’s easy to find DNA in the air, and some weird insect cybernetics.
🔥 Picks of the Week
News highlights in 3 minutes.
1/ First CRISPR’d Food to Hit U.S. Market
Pairwise wants you to eat more mustard greens. Or kale. Or maybe cabbage.
Huh? They’re all basically the same thing?
The company has used CRISPR gene editing to remove the ‘pungent’ smell from mustard greens, which are more nutritious than other salad leaves, like romaine. Pairwise hopes more consumers will eat them if they don’t smell so bad.
The CRISPR’d mustard greens are being rolled out to a handful of restaurants in St. Louis, Minneapolis and Springfield, Massachusetts. Grocery stores in the Pacific Northwest will follow. This is the first commercialized, CRISPR’d food in the United States.
WIRED just wrote a story about this, but it’s sorta old news. Pairwise got the green light from the U.S.D.A. way back in August 2020, and Japan already offers a CRISPR-edited plant in grocery stores: A tomato with boosted levels of GABA, a chemical signal in the brain. "The company behind the tomato, Sanatech Seeds, claims that eating GABA can help relieve stress and lower blood pressure," the WIRED article says.
And the article doesn’t mention how Pairwise engineered the mustard to be “less pungent.” It turns out that mustard greens have an enzyme called myrosinase. The genes that encode this enzyme are spread across seven chromosomes, and there are 17 copies of them. When you chew the leaves, myrosinase makes allyl isothiocyanate, the chemical culprit behind mustard’s punchy taste. (Radish and wasabi apparently have similar molecules.)
Pairwise used CRISPR-Cas12a to knock out all 17 copies of the myrosinase-encoding gene. Anyone who has worked with plants knows that this is an impressive feat. I also found articles that say Pairwise is working on at least 14 gene-edited fruits and vegetables, including blackberries without seeds and cherries without pits.
The company also has licensing deals with Tropic Biosciences to make bananas that don't brown as fast and coffee with naturally low caffeine & high solubility (for instant coffee). To be honest, I don’t fully understand the business decisions behind gene-edited mustard greens. People in the South, at least, seem to like the taste. But I totally understand the push toward bananas that don’t go brown quite so fast; it takes 1.3 kilograms of CO2 and 330 liters of water to make one kilo of bananas, and yet Americans throw away more than 700 million kilos every year.
Read more in WIRED.
2/ Your DNA is Everywhere. And It’s Easy to Find.
A study published Monday in Nature Ecology & Evolution shows that tiny amounts of human DNA, shed into the soil or air, can be easily detected using little more than a $1,000 Nanopore MinION. Researchers figured out a person’s medical conditions and ancestry using dirt collected from a place they had previously visited. That’s scary.
From The New York Times:
As a proof of concept…researchers scooped up a soda-can-size sample of water from a creek in St. Augustine, Fla. They then fed the genetic material from the sample through a nanopore sequencer, which allows researchers to read longer stretches of DNA…
The researchers recovered enough mitochondrial DNA — passed directly from mother to child for thousands of generations — to generate a snapshot of the genetic ancestry of the population around the creek, which roughly aligns with the racial makeup reported in the latest census data for the area…
They also found key mutations shown to carry a higher risk of diabetes, cardiac issues or several eye diseases. According to their data, someone whose genetic material turned up in the sample had a mutation that could lead to a rare disease that causes progressive neurological impairment and is often fatal. The illness is hereditary and may not emerge until a patient’s 40s. Dr. Duffy couldn’t help but wonder — does that person know? Does the person’s family? Does the person’s insurance company?
Scientists need to obtain permission from a university ethics board before they trek out into the woods and search for DNA. Law enforcement officials don’t. They can just do it.
Some of the most interesting details from the paper didn’t make it into the New York Times article, either. Like this one: Researchers recovered strands of DNA that were “up to 148,969 [base pairs] long,” and also found a piece of mitochondrial DNA that was 16,535 bases long, which is “only 34 bp shorter than the full-length mitochondrial reference genome.” DNA from the air gave the longest reads. In other words, you shed DNA all the time, and it doesn’t really break down as fast as you might think in dirt, sand, or the air.
Read more in The New York Times.
3/ How to Stop the Death Cap Mushroom
CRISPR was used to discover an antidote for death cap mushrooms. The approach is clever: Use “CRISPR-Cas9 gene-editing technology to create a pool of human cells, each with a mutation in a different gene.” Then, test “which mutations helped the cells to survive exposure to α-amanitin,” the death cap toxin.
A Chinese group of scientists quickly homed in on an enzyme, called STT3B, that normally coats proteins with sugar molecules. This enzyme is required for α-amanitin’s toxicity. They showed that it’s possible to shut down this interaction via a commercially-available chemical, called indocyanine green, which inhibits STT3B; an antidote.
The Nature article mentions that this approach — mutate a bunch of cells, bathe them in poison, and pull out the cells that survive — had previously been used to discover an antidote for box jellyfish venom. But I also found papers that did the same to discover how Shiga-like toxins and ricin (once used to assassinate a Bulgarian dissident, in 1978) kill cells. Is there anything CRISPR can’t do?
Read more in Nature.
📤 In the News
Other quick-hit news items you might have missed.
A gene therapy for Duchenne muscular dystrophy is (probably) on the way. But the whole story is weird. On May 12, the FDA said that “the clinical studies conducted to date do not provide unambiguous evidence that SRP-9001 is likely beneficial for ambulatory patients with DMD.” Then — that same day — an advisory panel voted 8-6 to recommend approval for the gene therapy anyway. Oh, to be a fly on the wall. (link)
Ada Nguyen published a great guide on the longevity biotech landscape. (link)
Also in aging news: New Limit launches with $40M. They are mainly using epigenetic editing to explore aging, and how to roll it back. (link)
Phage therapies — antibiotics’ long-lampooned little brother — are making a resurgent comeback. (link)
Yup, Elizabeth Holmes is going to prison. Maybe for real this time? (link)
An mRNA vaccine for many types of flu viruses is now in a phase I clinical trial. If this works, it’s a big deal! No more designing new flu vaccines each year? (link)
Amgen is sad that the Federal Trade Commission did not let them buy Horizon Therapeutics for $27.8 billion. (link)
A company that made a chicken breast from fungal proteins is now an XPRIZE finalist and could win the $15M prize. Cool. (link)
Nicole Paulk, a professor at UCSF and a really successful AAV engineer, just launched Siren Bio. The company will use gene therapies (with engineered viruses) to attack solid tumors. (link)
Cadence, a company that uses pulses of electricity to alleviate biomarkers of epilepsy, raised a $26 million series B. (link)
DiogenX, a company that uses a recombinant protein to “regenerate” insulin-producing beta cells for diabetics, raised €27.5M in a series A. (link)
NewBiologix launches with $50M to manufacture AAVs for gene therapies. (link)
A Flagship Pioneering company, called Metaphore, launches with $50M to develop drugs based on biomimicry. The whole article is confusing. Read at your own peril! (link)
Prevail Therapeutics (owned by Eli Lilly) is trying to make genetic medicines for neurological diseases. They’ve now signed a deal for exclusive rights to Scribe Therapeutics’ CRISPR-editing tools. It could be worth $1.5 billion if a bunch of milestones are met. (link)
🧠 Musings
Fun stuff that has little to do with biotech.
Some fragile scrolls, unearthed from the volcanic ash of Herculaneum after the eruption of Mount Vesuvius, are now being unrolled. Just a few years ago, similar scrolls disintegrated immediately upon being opened. This is part of the $1,000,000 Vesuvius Challenge. For more details on the challenge and why this matters, see the Lunar Society podcast with Nat Friedman. It’s really interesting. (link)
An interactive “period table of precision fermentation.” Engineered cells are already making vanilla, resveratol, and so much more. (link)
Ink derived from an octopus can move “dyed particles in response to light,” thus changing colors to match its surroundings. Camouflage. Cool. (link)
The Netherlands has finally finished building a facility to train scientists how “to prevent, spot and respond to chemical warfare.” The hazmat suits, at least, are hilarious. (link)
Sydney Brenner was a talented writer. Recommend. (link)
📈 Data Brief
One chart about biology and our world.
In 1990, a four-year-old girl name Ashanti DeSilva became the first person to be cured by gene therapy. DeSilva had adenosine deaminase deficiency, which damaged her immune system and made it difficult to fight off even common infections. Scientists removed Ashanti’s blood cells and inserted a functional copy of the ADA gene via a virus. The blood cells were then given back to DeSilva and, within six months, her immune system returned to normal.
Jesse Gelsinger’s story is more tragic. He died in 2000 after receiving a gene therapy for a rare metabolic disorder. His body “had an intense inflammatory response” and he “developed a dangerous blood-clotting disorder, followed by kidney, liver, and lung failure. Four days after receiving the shot Jesse was declared brain dead and taken off life support.” The clinical trial was halted and 69 others were investigated. James Wilson, director of the institute where the trial took place, was stripped of his titles. Wilson then went on to isolate AAV9 for the first time, and it was later used to develop one of the first FDA-approved gene therapies: Zolgensma.
⚒️ Note of the Week
On companies and underrated ideas.
Put a microchip into an insect cocoon and the butterfly will emerge with electronics hardwired into its brain. (link)
See you next week! In the meantime, find me on Twitter or LinkedIn.
— Niko McCarty
Disclosure: The views expressed in this blog are entirely my own and do not represent the views of any company or university with which I am affiliated.