The Problem with Darling 58

May 28, 2024 3:16 PM

Saving the American Chestnut continues to be difficult. A breakthrough in genetic engineering was intended to bring them back and transform the science of species restoration while potentially netting its inventors millions of dollars and wide acclaim. Instead, a mix-up in the lab has sparked a veritable civil war in the niche conservation community.
posted by emjaybee (19 comments total)

This is really sad. I really expected this to be successful and that I would get to see chestnuts. There are still decomposing enormous trunks in the woods in places. There are still little baby trees that pop up and live a few years before succumbing to the fungus. I really thought it was possible to bring them back.
posted by hydropsyche at 3:42 PM on May 28 [10 favorites]

Would like to read this, but I hit a paywall. Can you maybe summarize?
posted by OnceUponATime at 4:47 PM on May 28

Try this: https://archive.is/s9vJZ.

Archive.is is a reliable way to get to NYMag and associated sites when you hit a paywall.
posted by mediareport at 4:52 PM on May 28 [5 favorites]

I've read it twice now and I'm still not sure: Does Darlington 58 not exist? Seems like if they have 58 or the ability to make it this is only a setback that can be addressed by planting some 58 variety.
posted by Mitheral at 5:34 PM on May 28 [3 favorites]

It looks like they do not have 58. And from what I gather getting to 58 is not actually possible.
posted by 922257033c4a0f3cecdbd819a46d626999d1af4a at 5:41 PM on May 28

I really couldn't tell if they had once had 58 but had failed to breed it at all, if they once had 58 but the inserted mutation had not been passed down after accidental cross-breeding with 54, or if 58 had never actually existed.
posted by hydropsyche at 5:45 PM on May 28 [3 favorites]

My understanding is the lab work is so messed up the they have to start over and because trees grow slowly it will be a decade or more before they get to where they thought they were with Darling 58. There are other projects underway to create blight resistant trees. There is a backcross program in Virginia that has been working on a multi generation approach where they start with a trees that were half American / half Chinese and then each generation cross it with another American Chestnut until after many generations you have a tree that is almost all American Chestnut but with the blight resistance of the Chinese Chestnut. There is another project looking at ways to weaken the blight using biological controls like virus’ that infect the blight fungus and weaken it so the trees can recover.

It is sad because there are people who have worked their whole lives on this project and now in middle age they had hoped to see restored chestnut forests before they die.
posted by interogative mood at 6:15 PM on May 28 [8 favorites]

From the article it seems like there really was a Darling 58 tree, at least at one point:

In 2012, (Powell) landed on a version that seemed to convey total blight resistance without changing the American character of the trees. He dubbed the revelatory version Darling 58. ...

With Darling 58’s blight-resistance properties proven in the lab, and seedlings planted at carefully monitored test sites, it was just a matter of getting the government to deregulate Powell’s creation. ...

“The line that Tom has been using — that everyone has been using — was supposedly derived from Darling 58, and there was a good genetic map of the transgene on chromosome seven,” Tan says. But when he couldn’t find that gene on any of Klak’s samples, he started to wonder if they all might have the wrong tree.

So it seems like there was a tree that had blight resistance and was analyzed in the lab and genetically mapped, but that the trees that got distributed were not versions of that tree.

If that tree still exists and is still producing pollen it seems like this would just be a setback. Of course that's just my uninformed interpretation on what is in this article.
posted by Reverend John at 6:25 PM on May 28 [3 favorites]

I have spent some time off and on in the summers since the 1970s outside of Asheville, North Carolina. I remember being shown chestnut saplings growing from the roots of long dead stumps (perhaps at the Cradle of Forestry) and being told they looked healthy now, but would soon succumb to the blight. Made a real impression on pre-teen me. Ever since then I have checked in from time to time on efforts to bring the American chestnut back, but progress has always been slow at best. But even if someone succeeds in creating a blight resistant tree, I can’t imagine it ever returning to its former place in the ecosystem. How would you even introduce a new tree into mature forests? And where I live, “forest” often refers to row after row of loblolly pines planted by timber companies decades ago. But as much of a forest as a wheat field is a grassland. Who will profit from putting chestnuts back into the forest? Is it more likely they will be grown on tree farms, and possibly cut down if they are found outside of an approved location? There is precedent for such things. But at my age, as alluded to above, I am unlikely to live long enough to see how it plays out. I do wish I could see a forest with 100 foot tall chestnuts scattered throughout.
posted by TedW at 6:45 PM on May 28 [3 favorites]

Some more info
https://tacf.org/darling-58/

I'm still a tad confused on why/where Darling 58 is.
posted by 922257033c4a0f3cecdbd819a46d626999d1af4a at 6:46 PM on May 28

Ahh here we go

Why not then return to the “real” Darling 58? The first reason is that the Darling 58 also uses the 35S constitutive promoter which appears to result in a variety of metabolic costs to the tree and likely causes the majority of performance problems observed in the Darling line. Secondly, there are only a handful, and perhaps even only one, D58 tree(s) in existence. These trees are at either the T0 or T1 stage (the original event and first-generation offspring). If work is to start over at those early diversification stages, it makes sense to focus on new OxO lines that express the gene only in tissues infected with blight. Confining OxO expression to blight infected tissues should reduce the metabolic cost of expressing this gene, thus these new lines are more likely to have enhanced forest competitiveness.

from https://tacf.org/darling-58/
posted by 922257033c4a0f3cecdbd819a46d626999d1af4a at 6:59 PM on May 28 [11 favorites]

Oh, damn. I almost did my PhD on the historical ecology of American chestnut, and am still somewhat sad I went down a different path. I think about American chestnut, and the blight, every time in the woods. Of course, around here, it's hard not to be reminded of it with all of the dead ash trees recently killed by emerald ash borer.
posted by mollweide at 7:24 PM on May 28 [3 favorites]

This makes me so sad. The street I grew up on had a canopy of Chestnut trees arching across the street with such an an effect a picture of the street became a postcard. It was beautiful. I know a bit about the program in Virginia and I'm hopeful that, perhaps not in my lifetime, someday the Chestnut will be restored.
posted by bluesky43 at 7:29 PM on May 28 [3 favorites]

TACF says there are other transgenic Chestnut projects they are funding and that those trees show more promise. They also have a back cross breeding program where they started with a hybrid 50% American and 50% Chinese chestnut and then every generation pick the ones that show the most promise for American characteristics and blight resistance and then cross them with an American Chestnut and repeat. The goal is after several generations to have a tree that is 95-98% American Chestnut but with the blight resistance of the Chinese trees. That was the original approach they started with in 1989 when genetic engineering was not seen as feasible. They are testing the generation of trees now that might be useful for restoration. The advantage of this approach is that the trees won’t require the USDA and FDA approvals of the transgenic approach.

Of course the difficulty of the research in these areas is that trees take a long time to grow. Regardless of how you get the genes in there for blight resistance you have to make sure you get a tree that is tall and straight like the old giant American chestnut trees we lost. That requires a long time to verify.
posted by interogative mood at 10:43 PM on May 28 [1 favorite]

compare/contrast ESF's "A Message to Supporters of The American Chestnut Research and Restoration Project" to NYMag:

Article: Last spring, while foundation scientists in the field were wondering what could be wrong with the trees, Thomas Klak, an environmental-science professor at the University of New England in Portland, Maine, was struggling to produce Darling 58 plants with two copies of the OxO gene. He reached out to Ek Han Tan, a geneticist at the University of Maine who developed a test to analyze their genome. [...] In October 2023, Klak and Tan broke the news to Newhouse and his ESF colleagues. Newhouse says ESF began working to confirm, as initial tests weren’t “entirely consistent” with the hypothesis that the trees were Darling 54. Nearly a month later, after following up repeatedly with the ESF team, Tan looped in the foundation’s science director. It was the first the foundation had heard of the major mix-up.

ESF update, para 2 acknowledges the foundation "made a unilateral decision late last year to cease working with us on Darling. We do not agree with this decision and feel it would be in the best interest of American chestnut restoration for all interested parties to work together to find solutions."
Para 3: In late 2023, ESF discovered a labeling error between two Darling varieties (54 and 58) that were developed at the same time. The labeling is being corrected and new procedures are in place to ensure it does not happen again. We immediately contacted regulators about the situation and are following their guidance for submitting updates. We have acknowledged this clerical error and have accepted responsibility. It is important to recognize that it does not impact our results to date, the pursuit of regulatory approval, safety of the trees, our continued research or ESF’s commitment to restoring the American chestnut.

TACF partnered up with ESF in 1989, was the project's primary backer for ages, and had to hear about this debacle from the Maine geneticist. ESF, focused on the "American Castanea" deal & the recent USDA grant, "immediately" contacted regulators [the FDA and EPA, as in the article].
posted by Iris Gambol at 12:00 AM on May 29 [1 favorite]

Also, it appears I've misunderstood the meaning of "unilaterally" for decades.

Article: “To this day, we’ve never heard anything directly from ESF,” says Pitt, the American Chestnut Foundation’s president.
ESF update: ESF continues to work closely with a number of organizations including the New York Chapter of TACF

A schism in a small foundation (in December 2023, a Washington Post article puts the foundation's membership at 5,000), with its New York chapter likely the largest fundraising arm? Superb. But tensions have been simmering, since, oh, at least last spring.

March 7, 2023, ESF's "About" page for the project, archived link:
Members of the national organization The American Chestnut Foundation approached Dr. William Powell and Dr. Charles Maynard of SUNY ESF in 1989

March 23, 2023, ESF's "About" page for the project, archived link: Founding members of the New York Chapter of The American Chestnut Foundation approached Dr. William Powell and Dr. Charles Maynard of SUNY ESF in 1989
posted by Iris Gambol at 1:01 AM on May 29 [1 favorite]

That TACF explainer about the falling out, where "American Chestnut Research and Restoration Project SUNY-ESF" [ESF] = ACRRP, has a fairly sus detail, if the timeline ties out: Over the past 11 years, TACF has provided more than $2 million in funding to the ACRRP for their work on transgenic American chestnuts. Additional assistance, also valued at approximately $2 million, in the form of expert legal counsel, experimental design and testing, and general outreach, have provided crucial support and guidance to ACRRP in its applications to deregulate D58. [...] As reported in the Washington Post, TACF was surprised to learn in mid-2022 that directors of the ACRRP had engaged with private investors who formed a company, American Castanea Inc., to commercialize production of the Darling tree (now known to be D54).

The TACF link to the WaPo article published Dec. 24, 2023 (archived link) contains no mention of American Castanea, only: "The American Chestnut Foundation grew concerned, too, about SUNY ESF’s interest to use a for-profit company to eventually grow seeds, a move the school meant to help scale up distribution but one that ran counter to the foundation’s nonprofit mission."

NYMag has Powell and [longtime protégé] Newhouse meeting with "American Castanea, a newly formed company whose founders saw a huge opportunity in meeting the intense demand for seedlings they expected to follow deregulation."

Dr. Powell was diagnosed with colon cancer in August 2022, and underwent months of chemotherapy. The cancer spread. By June 2023, he'd retired as lab director and passed the baton to Newhouse (assistant director, in September 2022; co-director in December 2022). Powell died in November 2023.

The TACF wording on its site makes it seem like directors at ESF "engaged with private investors" — something the foundation learned about in "mid-2022" — which led to the formation of the for-profit American Castanea. American Castanea, Inc. is a Delaware Domestic Corporation filed on November 15, 2022.
posted by Iris Gambol at 2:15 AM on May 29 [5 favorites]

That FAQ is really helpful, 922257033c4a0f3cecdbd819a46d626999d1af4a. The detail that homozygous D54 is a lethal genotype suggests that this line would likely be ineffective at viably reproducing in the wild (1/4 of offspring would be lethal homozygous D54, and 1/4 of offspring would be homozygous susceptible to the fungus) and likely would always primarily rely on greenhouse breeding. Which is great if you're the for-profit company marketing the trees. Yikes.
posted by hydropsyche at 3:20 AM on May 29 [4 favorites]

Yes, I just started a case study for my intro bio students' Mendelian genetics module on this. We do way too many examples of human genetic conditions, and I always worry that I'm going to traumatize some poor kid who has Huntington's in their family. This will be a great change of pace.
posted by hydropsyche at 3:32 AM on May 29 [10 favorites]