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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.
Emotional intelligence is a skill sought by many employers. Here's how to raise yours.
- Daniel Goleman's 1995 book Emotional Intelligence catapulted the term into widespread use in the business world.
- One study found that EQ (emotional intelligence) is the top predictor of performance and accounts for 58% of success across all job types.
- EQ has been found to increase annual pay by around $29,000 and be present in 90% of top performers.
Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.
- Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
- They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
- The research raises many ethical questions and puts to the test our current understanding of death.
What's dead may never die, it seems<p>The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called Brain<em>Ex</em>. Brain<em>Ex </em>is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.</p><p>Brain<em>Ex</em> pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.</p><p>The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if Brain<em>Ex</em> can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.</p><p>As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.</p><p>The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.</p><p>"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told <em><a href="https://www.nationalgeographic.com/science/2019/04/pig-brains-partially-revived-what-it-means-for-medicine-death-ethics/" target="_blank">National Geographic</a>.</em></p>
An ethical gray matter<p>Before anyone gets an <em>Island of Dr. Moreau</em> vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.</p><p>The Brain<em>Ex</em> solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness. </p><p>Even so, the research signals a massive debate to come regarding medical ethics and our definition of death. </p><p>Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?</p><p>"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told <a href="https://www.nytimes.com/2019/04/17/science/brain-dead-pigs.html" target="_blank">the <em>New York Times</em></a>. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."</p><p>One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.</p><p>The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, <a href="https://www.nature.com/articles/d41586-019-01216-4#ref-CR2" target="_blank">told <em>Nature</em></a> that if Brain<em>Ex</em> were to become widely available, it could shrink the pool of eligible donors.</p><p>"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.</p><p>It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.</p><p>Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? <a href="https://bigthink.com/philip-perry/after-death-youre-aware-that-youve-died-scientists-claim" target="_blank">The distress of a partially alive brain</a>? </p><p>The dilemma is unprecedented.</p>
Setting new boundaries<p>Another science fiction story that comes to mind when discussing this story is, of course, <em>Frankenstein</em>. As Farahany told <em>National Geographic</em>: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have <em>Frankenstein</em>, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."</p><p>She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.</p>
A 71% wet Mars would have two major land masses and one giant 'Medimartian Sea.'
- Sci-fi visions of Mars have changed over time, in step with humanity's own obsessions.
- Once the source of alien invaders, the Red Planet is now deemed ripe for terraforming.
- Here's an extreme example: Mars with exactly as much surface water as Earth.
Misogynists in space<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU1ODkzMS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNDEzMzY4OX0.XEEPJJnp75idUXzutmJ5ZGo35WYKxmVEyIiSwDpMeE4/img.jpg?width=980" id="6c715" class="rm-shortcode" data-rm-shortcode-id="2210c6d8590f7886eb6e4a89bcd6a50e" data-rm-shortcode-name="rebelmouse-image" alt="\u200bMars \u2013 and Martians \u2013 were a staple of 1930s pulp science fiction." />
Mars – and Martians – were a staple of 1930s pulp science fiction.
Image: ScienceBlogs.de - CC BY-SA 2.0<p><em>"Oh, my God, it's a woman," he said in a tone of devastating disgust. </em></p><p><em></em>"Stowaway to Mars" hasn't aged well. First serialised in 1936 as "Planet Plane" and set in the then distant future of 1981, the fourth novel by sci-fi legend John Wyndham (writing as John Benyon) could have been remembered mainly for its charming retro-futurism, if it weren't so blatantly, offhandedly misogynistic. </p><p>Fortunately, each era's sci-fi says more about itself than about the future. That also goes for how we see Mars. 'Classic' Martians, like the ones in H.G. Wells' "War of the Worlds," are creatures from a dying planet, using their superior firepower to invade Earth and escape their doom. That trope reflected 19th- and 20th-century fears about mechanized total warfare, which hung like a sword of Damocles over otherwise increasingly placid lifestyles. </p><p>Closer inspection of the Red Planet has revealed the absence of green men; and now <em>we're </em>the dying planet – pardon my Swedish. So the focus has shifted from interplanetary war to terraforming the fourth rock from the Sun, creating something all those protest signs say we don't have: a Planet B. <span></span></p>
How to keep Mars from killing us<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU1ODkzNC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzOTgyNTcwNX0.V7I3VFPch0oV8YDx95ZLLZFY7zEcyqSiG5uCAiMu2hg/img.jpg?width=980" id="f092e" class="rm-shortcode" data-rm-shortcode-id="5ca3b60a81a5f003a3e1ef467cf95f1a" data-rm-shortcode-name="rebelmouse-image" alt="Map of the surface of the planet Mars, showing the ice caps at the poles." />
Mars today: red and dusty, dead and deadly.
Image: NASA - public domain.<p>Cue Elon Musk, who doesn't just build Teslas but also heads SpaceX, a program to make humanity an interplanetary species by landing the first humans on Mars by 2024 as the pioneers of a permanent, self-sufficient and growing colony.</p><p><span></span>Such a colony would benefit from an environment that doesn't try to kill you if you take off your space helmet. Martian temperatures average at around -55°C (-70°F), and its atmosphere has just 1 percent the volume of Earth's, in a mix that contains far less oxygen. Changing all that to an ecosystem that's more like our own, would be a herculean task. </p>
From Red Mars to Green Mars<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU1ODk0NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTE0NjA5N30.iloUVThQOBjnkP7HuLefzPlOeIDE8wOlfcXMQ7ZYDMw/img.jpg?width=980" id="f9ad2" class="rm-shortcode" data-rm-shortcode-id="05032082590ebcf98a6830576ae3815e" data-rm-shortcode-name="rebelmouse-image" alt="\u200bBefore and after images of a terraformed Mars" />
Before and after images of a terraformed Mars in the lobby of SpaceX offices in Hawthorne, California.
Image: Steve Jurvetson / Flickr - CC BY 2.0<p>So how would Musk go about it? In August 2019, he launched a t-shirt with the two-word answer: 'Nuke Mars'. The idea would be to heat up and release the carbon dioxide frozen at Mars's poles, creating a much warmer and wetter planet – as Mars may have been about 4 billion years ago – though still not with a breathable atmosphere.</p><p>Alternatives to nuclear explosions: photosynthetic organisms on the ground or giant mirrors in space, either of which could also melt the Martian poles. However, many scientists question the logistics of these plans, and even whether there is enough readily accessible CO2 on Mars to fuel the climate change that Musk (and others) envision. </p><p>Ah, but why stop at the objections of the current scientific consensus? Sometimes, you have to dream ahead to see the place that can't be built yet. In the lobby of SpaceX HQ in Hawthorne, California, Red Mars and Green Mars are shown side by side. The terraformed version on the right looks green and cloudy and blue – Earth-like, or at least habitable-looking.<span></span></p>
Or how about a Blue Mars?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU1ODk1MS9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTYwNTkwNjU4OX0.sdccROyaHpYcw9C8E-4iICzMA_GNXsZXzL1XGcqDink/img.png?width=980" id="1ba6e" class="rm-shortcode" data-rm-shortcode-id="b3325bff53cb4b13cf77bff877961338" data-rm-shortcode-name="rebelmouse-image" alt="wet Mars map" />
A map of Mr Bhattarai's wet Mars, in the Robinson projection.
Image: A.R. Bhattarai, reproduced with kind permission; modified with MaptoGlobe<p>But why stop there? This map looks forward to a Mars that doesn't just have some surface water, but exactly as much as Earth – which means quite a lot. No less than 71 percent of our planet's surface is covered by oceans, seas, and lakes. The dry bits are our continents and islands. </p><p><span></span>In the case of Mars, a 71 percent wet planet leaves the planet's northern hemisphere mainly ocean, with most of the dry land located in the southern half. </p><p><span></span>Most of the dry land is connected via the south pole but is articulated in two distinct land masses. Both semi-continents are separated by a wide bay that corresponds to Argyre Planitia. </p><p><span></span>The one in the west is centered on Tharsis, a vast volcanic tableland. To the north, attached to the main land mass, is Alba Mons, the largest volcano on Mars in terms of area (with a span comparable to that of the continental United States). </p><p><span></span>It's about 6.8 km (22,000 ft) high, which is about one-third of Olympus Mons, a volcano now located on its own island off the northwest coast of Tharsis. At a height of over 21 km (72,000 ft), Olympus Mons is the highest volcano on Mars and the tallest planetary mountain (1) currently known on the solar system. Olympus rises about 20 km (66,000 ft) above the sea level as shown on this map.</p>
A new civilization<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU1ODk1Ni9vcmlnaW4uZ2lmIiwiZXhwaXJlc19hdCI6MTYyMDEwNzQ0Nn0.vKa0nNqKdMTfWYG6behUPPg9giToq3Lx6CsWQ70eqCE/img.gif?width=980" id="7f62c" class="rm-shortcode" data-rm-shortcode-id="bcffffaf301663a42758cf4cb8e11a76" data-rm-shortcode-name="rebelmouse-image" alt="\u200bSpinning globe view of Mr Bhattarai's wet Mars." />
Spinning globe view of Mr Bhattarai's wet Mars.
Image: A.R. Bhattarai, reproduced with kind permission; modified with MaptoGlobe<p>Mars's eastern continent is centered not on a plateau, but on a depression that on today's 'dry' Mars is called Hellas Planitia, one of the largest impact craters in the Solar system. On the 'wet' Mars of this map, the crater is the central and largest part of a sea that is surrounded by land, a Martian version of the Mediterranean Sea. Perhaps one day this Medimartian Sea will be the Mare Nostrum of a new civilization. </p><p>To the northeast of the circular semi-continent is a large island that on 'our' Mars is Elysium Mons, a volcano that is the planet's third-tallest mountain (14.1 km, 46,000 ft).</p><p>The map is the work of Aaditya Raj Bhattarai, a civil engineering student at Tribhuvan University in Kathmandu (Nepal). Talking to <a href="https://www.inverse.com/innovation/mars-with-water-map" target="_blank" rel="dofollow">Inverse</a>, he said he hoped his map could help further the Martian plans of Elon Musk and SpaceX: "This is part of my side project where I calculate the volume of water required to make life on Mars sustainable and the sources required for those water volumes from comets that will come nearby Mars in the next 100 years."<br></p><p><br></p><p><strong></strong><em>Images by Mr Bhattarai reproduced with kind permission. Check out <a href="https://aadityabhattarai.com.np/" target="_blank">his website</a>. </em><em>Planetary projection and spinning globe created via <a href="https://www.maptoglobe.com/" target="_blank">MaptoGlobe</a>.</em></p><p><strong>Strange Maps #1043</strong></p><p><em>Got a strange map? Let me know at </em><a href="mailto:firstname.lastname@example.org">email@example.com</a><em>.</em></p><p>________<br>(1) The tallest mountain in the Solar system, planetary or otherwise, we know of today, is a peak which rises 22.5 km (14 mi) from the center of the Rheasilvia crater on Vesta, a giant asteroid which makes up 9 percent of the entire mass of the asteroid belt. <br></p>
Starting and running a business takes more than a good idea and the desire to not have a boss.
- Anyone can start a business and be an entrepreneur, but the reality is that most businesses will fail. Building something successful from the ground up takes hard work, passion, intelligence, and a network of people who are equally as smart and passionate as you are. It also requires the ability to accept and learn from your failures.
- In this video, entrepreneurs in various industries including 3D printing, fashion, hygiene, capital investments, aerospace, and biotechnology share what they've learned over the years about relationships, setting and attaining goals, growth, and what happens when things don't go according to plan.
- "People who start businesses for the exit, most of them will fail because there's just no true passion behind it," says Miki Agrawal, co-founder of THINX and TUSHY. A key point of Agrawal's advice is that if you can't see yourself in something for 10 years, you shouldn't do it.
After a decade of failed attempts, scientists successfully bounced photons off of a reflector aboard the Lunar Reconnaissance Orbiter, some 240,000 miles from Earth.