Serious problem found with gene-edited celebrity cows

The FDA calls out creators of genetically tweaked hornless bulls.

Hornless bulls would look a lot like this cow.

Image source: prochasson frederic/Shutterstock
  • Hornless bull clones turn out to have questionable genomes.
  • Scientists were so confident they didn't even look for transgenic DNA.
  • No one's sure what to do with the offspring.

Given how new direct editing of genes is — as opposed to cross-breeding — it's not surprising that unexpected complications will arise. What is surprising is the degree of confidence some scientists have in their gene-editing knowledge and skills, and thus the safety of their experimentation. No one's really sure yet, for example, if China's He Jiankui really did illegally produce genetically modified twin girls in China last year.

We do know, however, that in 2015, a Minnesota company, Recombinetics , announced that they'd successfully cloned five hornless bulls from gene-edited bovine embryo fibroblasts. Two of the bulls, Spotigy and Buri, became poster children for the wonders of gene editing. Now, according to a new investigation by the FDA, the simple, clean gene splice Recombinetics claimed to have performed was neither. The cattle — Buri has 17 offspring while Spotigy was euthanized for tissue study — possess two antibiotic-resistant genes as well as surprising bits of bacterial DNA.

The arrival of Spotigen and Buri

Image source: ANGHI/Shutterstock/Big Think

Recombinetics' bulls were heralded examples of gene modification's potential. Farmers regularly "poll" cows — that is, remove their horns— in a painful, difficult process aimed at preventing accidental injuries in herds and the humans that tend them.

The company used TALENs gene editing ("Transcription Activator-Like Effector Nucleases) to swap out a section of about 200 genes from a Holstein dairy bull for genes from a hornless one.

DNA editing involves cutting DNA with enzymes called nucleases targeted at the desired location in a cell's genome. Nucleases are proteins, which are hard to work with, so many researchers — including Recombinetics' — instead introduce plasmids, circular mini-chromosomes that code for the required "scissor." This causes the target cell to produce the nucleases itself, sparing the scientists the complexities of dealing with unstable protein.

In the case of Recombinetics' bulls, the plasmids also contained the replacement hornless DNA for insertion at the cut. Coming along for the ride — unknown to Recombinetics — was transgenic DNA, including the antibiotic-resistant genes and a handful of other things from a range of diverse microbes. This wouldn't necessarily have been a problem if the plasmids hadn't unexpectedly inserted themselves into the target cell's genome instead of simply delivering their payload and being done, as planned. Thus, adjacent to its edit site were 4,000 base pairs of DNA that from the plasmid.

Over-confident

Image source: wikimedia/U.S. Food and Drug Administration

At the time the editing was first announced, Recombinetics was very confident that what they'd produced was "100% bovine." "We know exactly where the gene should go, and we put it in its exact location," claimed Recombinetics to Bloomberg in 2017. "We have all the scientific data that proves that there are no off-target effects." In response to the latest findings, however, Tad Sontesgard of the Recombinetics subsidiary that owns the animals, admitted, "It was not something expected, and we didn't look for it." He acknowledges a more thorough examination of their work "should have been done."

Since genetically edited animals may be consumed, the FDA's position is that they likely require thorough testing and approvals. Recombinetics has publicly complained about such hurdles standing in the way of making animal genetic editing a routine occurrence. (They've also developed piglets that never hit puberty.) The company attempted to convince the Trump Administration to take genetically altered animals away from under the FDA.

How the problem was found

Image source: Moving Moment/Shutterstock

Not surprisingly, Recombinetics never applied for approval with the FDA, but Alison Van Eenennaam, their collaborator from University of California, Davis, did inform the FDA of their existence to facilitate exchanges of research insights and data.

Since the surviving edited cattle were being put up at Davis, Eenennaam started thinking about what to do with them. Incinerating experimental animals — and each of these weighs about a ton — costs 60 cents per pound. On the other hand, turning them into hamburger and steaks could reverse that cash flow. Her attempt to win the cows a food exemption from the FDA led to the discovery of the plasmids, though Sontesgard asserts they'd be safe to eat in either case.

And then there's milk. Brazil agreed to raise the first herd of genetically modified hornless dairy cows. Regulators there had even determined no exceptional oversight was going to be required.

Soon a bioinformatician from the FDA stumbled across the plasmid in a bull's genome. It's estimated that about half of Buri's 17 offspring also have it in theirs. The cows are now absolutely classified as genetically modified organisms, GMOs, not pure cow. Brazil has backed out.

Slowing their roll

Image source: Sergey Nivens/Shutterstock

As science moves forward a few steps, it often has to back up a step or two. Glimpsing a solution, especially to such a complex problem as genome editing, isn't the same as having one fully in hand, no matter how attractive the reward of getting there first may be, or how much money is to be made. We're on the edge of a new frontier here, and there are a growing number of similar tales. Scientists do need courage to stretch the boundaries of the known, yes, but humility is also a good idea.

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Photo: Luisa Conlon , Lacy Roberts and Hanna Miller / Global Oneness Project
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Experts are already predicting an 'active' 2020 hurricane season

It looks like a busy hurricane season ahead. Probably.

Image source: Shashank Sahay/unsplash
Surprising Science
  • Before the hurricane season even started in 2020, Arthur and Bertha had already blown through, and Cristobal may be brewing right now.
  • Weather forecasters see signs of a rough season ahead, with just a couple of reasons why maybe not.
  • Where's an El Niño when you need one?

Welcome to Hurricane Season 2020. 2020, of course, scoffs at this calendric event much as it has everything else that's normal — meteorologists have already used up the year's A and B storm names before we even got here. And while early storms don't necessarily mean a bruising season ahead, forecasters expect an active season this year. Maybe storms will blow away the murder hornets and 13-year locusts we had planned.

NOAA expects a busy season

According to NOAA's Climate Prediction Center, an agency of the National Weather Service, there's a 60 percent chance that we're embarking upon a season with more storms than normal. There does, however, remain a 30 percent it'll be normal. Better than usual? Unlikely: Just a 10 percent chance.

Where a normal hurricane season has an average of 12 named storms, 6 of which become hurricanes and 3 of which are major hurricanes, the Climate Prediction Center reckons we're on track for 13 to 29 storms, 6 to 10 of which will become hurricanes, and 3 to 6 of these will be category 3, 4, or 5, packing winds of 111 mph or higher.

What has forecasters concerned are two factors in particular.

This year's El Niño ("Little Boy") looks to be more of a La Niña ("Little Girl"). The two conditions are part of what's called the El Niño-Southern Oscillation (ENSO) cycle, which describes temperature fluctuations between the ocean and atmosphere in the east-central Equatorial Pacific. With an El Niño, waters in the Pacific are unusually warm, whereas a La Niña means unusually cool waters. NOAA says that an El Niño can suppress hurricane formation in the Atlantic, and this year that mitigating effect is unlikely to be present.

Second, current conditions in the Atlantic and Caribbean suggest a fertile hurricane environment:

  • The ocean there is warmer than usual.
  • There's reduced vertical wind shear.
  • Atlantic tropical trade winds are weak.
  • There have been strong West African monsoons this year.

Here's NOAA's video laying out their forecast:

But wait.

ArsTechnica spoke to hurricane scientist Phil Klotzbach, who agrees generally with NOAA, saying, "All in all, signs are certainly pointing towards an active season." Still, he notes a couple of signals that contradict that worrying outlook.

First off, Klotzbach notes that the surest sign of a rough hurricane season is when its earliest storms form in the deep tropics south of 25°N and east of the Lesser Antilles. "When you get storm formations here prior to June 1, it's typically a harbinger of an extremely active season." Fortunately, this year's hurricanes Arthur and Bertha, as well as the maybe-imminent Cristobal, formed outside this region. So there's that.

Second, Klotzbach notes that the correlation between early storm activity and a season's number of storms and intensities, is actually slightly negative. So while statistical connections aren't strongly predictive, there's at least some reason to think these early storms may augur an easy season ahead.

Image source: NOAA

Batten down the hatches early

If 2020's taught us anything, it's how to juggle multiple crises at once, and layering an active hurricane season on top of SARS-CoV-2 — not to mention everything else — poses a special challenge. Warns Treasury Secretary Wilbur Ross, "As Americans focus their attention on a safe and healthy reopening of our country, it remains critically important that we also remember to make the necessary preparations for the upcoming hurricane season." If, as many medical experts expect, we're forced back into quarantine by additional coronavirus waves, the oceanic waves slamming against our shores will best be met by storm preparations put in place in a less last-minute fashion than usual.

Ross adds, "Just as in years past, NOAA experts will stay ahead of developing hurricanes and tropical storms and provide the forecasts and warnings we depend on to stay safe."

Let's hope this, at least, can be counted on in this crazy year.

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