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Serious problem found with gene-edited celebrity cows
The FDA calls out creators of genetically tweaked hornless bulls.
- 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.
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.
A Mercury-bound spacecraft's noisy flyby of our home planet.
- There is no sound in space, but if there was, this is what it might sound like passing by Earth.
- A spacecraft bound for Mercury recorded data while swinging around our planet, and that data was converted into sound.
- Yes, in space no one can hear you scream, but this is still some chill stuff.
First off, let's be clear what we mean by "hear" here. (Here, here!)
Sound, as we know it, requires air. What our ears capture is actually oscillating waves of fluctuating air pressure. Cilia, fibers in our ears, respond to these fluctuations by firing off corresponding clusters of tones at different pitches to our brains. This is what we perceive as sound.
All of which is to say, sound requires air, and space is notoriously void of that. So, in terms of human-perceivable sound, it's silent out there. Nonetheless, there can be cyclical events in space — such as oscillating values in streams of captured data — that can be mapped to pitches, and thus made audible.
Image source: European Space Agency
The European Space Agency's BepiColombo spacecraft took off from Kourou, French Guyana on October 20, 2019, on its way to Mercury. To reduce its speed for the proper trajectory to Mercury, BepiColombo executed a "gravity-assist flyby," slinging itself around the Earth before leaving home. Over the course of its 34-minute flyby, its two data recorders captured five data sets that Italy's National Institute for Astrophysics (INAF) enhanced and converted into sound waves.
Into and out of Earth's shadow
In April, BepiColombo began its closest approach to Earth, ranging from 256,393 kilometers (159,315 miles) to 129,488 kilometers (80,460 miles) away. The audio above starts as BepiColombo begins to sneak into the Earth's shadow facing away from the sun.
The data was captured by BepiColombo's Italian Spring Accelerometer (ISA) instrument. Says Carmelo Magnafico of the ISA team, "When the spacecraft enters the shadow and the force of the Sun disappears, we can hear a slight vibration. The solar panels, previously flexed by the Sun, then find a new balance. Upon exiting the shadow, we can hear the effect again."
In addition to making for some cool sounds, the phenomenon allowed the ISA team to confirm just how sensitive their instrument is. "This is an extraordinary situation," says Carmelo. "Since we started the cruise, we have only been in direct sunshine, so we did not have the possibility to check effectively whether our instrument is measuring the variations of the force of the sunlight."
When the craft arrives at Mercury, the ISA will be tasked with studying the planets gravity.
The second clip is derived from data captured by BepiColombo's MPO-MAG magnetometer, AKA MERMAG, as the craft traveled through Earth's magnetosphere, the area surrounding the planet that's determined by the its magnetic field.
BepiColombo eventually entered the hellish mangentosheath, the region battered by cosmic plasma from the sun before the craft passed into the relatively peaceful magentopause that marks the transition between the magnetosphere and Earth's own magnetic field.
MERMAG will map Mercury's magnetosphere, as well as the magnetic state of the planet's interior. As a secondary objective, it will assess the interaction of the solar wind, Mercury's magnetic field, and the planet, analyzing the dynamics of the magnetosphere and its interaction with Mercury.
Recording session over, BepiColombo is now slipping through space silently with its arrival at Mercury planned for 2025.
Erin Meyer explains the keeper test and how it can make or break a team.
- There are numerous strategies for building and maintaining a high-performing team, but unfortunately they are not plug-and-play. What works for some companies will not necessarily work for others. Erin Meyer, co-author of No Rules Rules: Netflix and the Culture of Reinvention, shares one alternative employed by one of the largest tech and media services companies in the world.
- Instead of the 'Rank and Yank' method once used by GE, Meyer explains how Netflix managers use the 'keeper test' to determine if employees are crucial pieces of the larger team and are worth fighting to keep.
- "An individual performance problem is a systemic problem that impacts the entire team," she says. This is a valuable lesson that could determine whether the team fails or whether an organization advances to the next level.