CRISPR: Can we control it?

The potential of CRISPR technology is incredible, but the threats are too serious to ignore.

- Our ability to manipulate genes can be very powerful. It has been very powerful.

- This is going to revolutionize human life.

- Would the consequences be bad? And they might be.

- Every time you monkey with the genome you are taking a chance that something will go wrong.

- The technique could be misused in horrible ways.

- When I started this research project, I've kind of had this initial feeling of what have I done.

JENNIFER DOUDNA: CRISPR gene-editing technology is a tool that scientists can use to change the letters of DNA in cells in precise ways. So I like to use the analogy of a word processor on a computer. So we have a document, you can think about the DNA in a cell, like the text of a document that has the instructions to tell the cell how to grow and divide and become a brain cell or a liver cell, or develop into an entire organism. And just like in a document, the CRISPR technology gives scientists a way to go in and edit the letters of DNA. Just like we might cut and paste text in our document or replace whole sentences, even whole paragraphs or chapters. We can now do that using the CRISPR technology in the DNA of cells. CRISPR is an acronym that actually represents a sequence of DNA letters in the genomes of cells. It's found in bacteria and it was interesting to scientists originally because it's a bacterial immune system, a way that bacteria can fight viral infection. For scientists this is sort of really a gift that allows research to proceed very quickly in terms of understanding the genetics of cells and organisms but also provides a very practical way to solve problems. In clinical medicine, the opportunity to make changes to blood cells that would cure diseases like sickle cell anemia, a disease where we've understood the genetic cause for a long time. But until now there hasn't been a way to actually think about treating patients. And now with this technology, it's possible in principle to remove stem cells that give rise to blood cells in a person's body, make edits to those cells that would correct the mutation causing a sickle cell disease and then replace those cells to essentially give a patient a new set of cells that don't have the defect. It's one thing to talk about being able to remove mutations from the human population that cause genetic disease. And I think for many people that would be a desirable thing to do. On the other hand, I think it's a very different discussion to think about using a technology like this to create enhanced human beings. People that are taller or have a certain eye color or other kinds of physical or intellectual traits that might be considered desirable. And it sort of immediately brings up sort of the the whole area of eugenics and sort of access to technology. Who gets access, who pays for it, who decides, who decides whether or not to do such a thing, should companies be allowed to offer this as a service to parents who want to do this and if so, should they be regulated in some way? There's a lot of very interesting and challenging questions, I think that go along with that.

RICHARD CLARKE: The technique could be misused in horrible ways. It could be misused for example, to create biological weapons, to create new forms of threats to human beings. Threats for which we don't have any known antidote. Or it could simply be used to create human beings of far superior capability. Not just taking genes and removing defects, but adding new super capabilities. What if in the process of that kind of gene editing, we created a caste society, where some people were genetically designed to do menial tasks and didn't have the capability of doing anything else. And other people were designed to be the rulers, with huge IQs and the capability of understanding things beyond the pale for lesser humans.

RICHARD DAWKINS: The ability to edit our own genomes is one thing we ought to worry about. I'm not sure it's so much an ethical problem as a more practical problem. What would the consequences be? Would the consequences be bad? And they might be. I think it's worth noticing that long before CRISPR, long before we became capable of editing our genomes in any way, we have been editing the genomes of domestic animals and plants by artificial selection, not artificial mutation, which is what we're now talking about, but artificial selection. When you think that a pekinese is a wolf, a genetically modified wolf. Modified not by directly manipulating genes, but by choosing for breeding individuals who have certain characteristics, for example, small snub nose, et cetera, and making a wolf turn into a pekinese. Well, we've been doing that very successfully with domestic animals like dogs, cows, domestic plants, like maize, for a long time. We've never done that to humans or hardly at all, and Hitler tried it but it's never really been properly done with humans, I'm glad to say. So if we've never done that with humans with the easy way, which is artificial selection, it's not obvious why we would suddenly start doing it the difficult way, which is by direct genetic manipulation. There doesn't seem to be integrate eagerness to do it, over the last few centuries anyway.

STEVEN PINKER: People think that introducing traits into offspring is a form of eugenics and is on a slippery slide to Nazi-ism. I happen to think that that is a bogus ethical argument but it is by far the majority ethical argument. And in many countries, genetic enhancement is or will be illegal. And it's gonna take a huge force to overcome that. Just as cloning is illegal in virtually every country and when Dolly the sheep was cloned in 1997, there were confident predictions that there's nothing you could do to stop human cloning. It was just around the corner. And here we are almost 20 years later and it has not happened. Also the task of engineering high intelligence is turning out to be a lot harder than one might've thought. In the late nineties, it was thought, well, sooner or later we'll find some high IQ genes. They'll give you three or four points, you put in a handful of them and you get a much smarter baby. There was going to be the gene for musical talent and the gene for athletic coordination. We have every reason to believe that those traits are substantially heritable. We've known that for decades just because of twin and adoption studies. On the other hand, we also know that the genes responsible are going to... Each one of them is gonna have an incy wincy effect. And there are dozens, hundreds, maybe thousands of them. So making your child smart is not a question of putting in one high IQ gene. It may be a question of putting in a hundred genes or a thousand genes. Every time you monkey with the genome you are taking a chance that something will go wrong. Also those genes, the ones that we have identified and we've made enormous progress in, just a few years ago there was not a single gene you could point to that had a positive effect on intelligence. Now we can point to a few of them that have incy wincy effects, a third of an IQ point. But on the other hand, we identify them by their correlations with intelligence. We have no idea what they do. I mean, if you find that any of those genes is actually expressed in the brain then you've had a really good day as a scientist but to know what the totality of their effects are, positive and negative, is something that we're not gonna know for a long time, if ever, when you're talking about hundreds of thousands of genes. How do we know that one of those genes that raises your IQ by a third of a point, doesn't also increase your chance of epilepsy or schizophrenia or brain cancer. Would you think for that matter that parents are going to be willing to take such chances with the biological integrity of their children, that in exchange for an increase of an IQ point or two, they're going to take some unknown risk of making the child schizophrenic or bipolar or some other disease that we may not know of, whose probabilities we don't know. Not so clear that they will.

SIDDHARTHA MUKHERJEE: The road to eugenics was paved with the best intentions and it was a series of, you can almost see the world tipping towards horror. Step by step by step. It seemed like one iterative step didn't seem that much. And yet, as you've accumulated all of these very soon you went from in Nazi Germany, in particular, starting with trying to eliminate or sterilize those who were somehow physically different from others. All the way, including folks who are deaf, folks who had various neurological diseases and then sort of marched inexorably towards other forms of identity, including obviously, Jews, gypsies, homosexuals, and so forth. So it's worthwhile remembering that that progression that occurred in the 1930s was perceived by citizens at that time as part of a progression. So it's incredibly important to remember that history when we step, as we are going to, as we're stepping towards the genetic modification of human embryos or even to some extent the genetic modification of other animals or plants, we have to remember that it seems as if there's a progression but all of a sudden, by the time from the beginning till the end, you may land up in a very different place. It's important also not to throw, as we enter new genetic technologies, not to throw the baby out with the genetic bathwater. I mean, it's important to remember that our ability to manipulate genes can be very powerful. It has been very powerful.

CLARKE: This is going to revolutionize human life. It's already beginning. It's going to mean that all of the genetic defects that have caused so much pain and suffering for people for millions of years, all of that could potentially be removed. So why does the great woman who invented this wake up in the middle of the night worrying about it.

DOUDNA: When I started this research project, we were certainly not thinking about a technology that would allow alteration of human evolution or anything of that nature. And over the last few years, as this technology has begun to be deployed globally for different applications, I've found that I have gone from thinking about it initially, just with sort of almost wide-eyed excitement thinking about all the opportunities that this offers, to realizing that there was real risk and that we really needed, we meaning the scientific community and really frankly the human community, needed to be aware of this and discussing it. And one of the things that sort of brought that to the forefront of my mind was a dream that I had, fairly early on, in which I walked into a room and a colleague of mine said to me, "Jennifer, I'd like you to explain the CRISPR technology to a friend." And he brought me into a room and a person was sitting with their back to me. And as they turned around, I realized with sort of a horror that it was Hitler. And it was actually Hitler with a sort of a pig nose and it almost looked like a chimeric pig-human sort of creature. And it sounds funny in a way to relate that image, but in the dream it was a terrifying thing. And I really felt real, just stone cold fear in the dream and sort of woke up from that dream with a start and realized, I've kind of had this initial feeling of what have I done. And that was really one of the things that motivated me to get out of the lab and start talking to people more broadly about the technology, about its capabilities, about the great things about it, but also about things that really required really a deep thought and careful consideration and regulation. I think with any new technology, one always has to try to get the balance right. On the one hand, we of course wanna see technologies and science in general being used to solve real world problems, real human problems. But on the other hand, we want to ensure that that progress is responsible progress, that we are working together with the stakeholders to ensure that there's not an unintended or even a negative intended consequence of the use of these technologies. How to do that is a big challenge.

  • CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary technology that gives scientists the ability to alter DNA. On the one hand, this tool could mean the elimination of certain diseases. On the other, there are concerns (both ethical and practical) about its misuse and the yet-unknown consequences of such experimentation.
  • "The technique could be misused in horrible ways," says counter-terrorism expert Richard A. Clarke. Clarke lists biological weapons as one of the potential threats, "Threats for which we don't have any known antidote." CRISPR co-inventor, biochemist Jennifer Doudna, echos the concern, recounting a nightmare involving the technology, eugenics, and a meeting with Adolf Hitler.
  • Should humanity even have access to this type of tool? Do the positives outweigh the potential dangers? How could something like this ever be regulated, and should it be? These questions and more are considered by Doudna, Clarke, evolutionary biologist Richard Dawkins, psychologist Steven Pinker, and physician Siddhartha Mukherjee.

7 most notorious and excessive Roman Emperors

These Roman Emperors were infamous for their debauchery and cruelty.

1876. Painted by Henryk Siemiradzki.
Politics & Current Affairs
  • Roman Emperors were known for their excesses and violent behavior.
  • From Caligula to Elagabalus, the emperors exercised total power in the service of their often-strange desires.
  • Most of these emperors met violent ends themselves.

We rightfully complain about many of our politicians and leaders today, but historically speaking, humanity has seen much worse. Arguably no set of rulers has been as debauched, ingenious in their cruelty, and prone to excess as the Roman Emperors.

While this list is certainly not exhaustive, here are seven Roman rulers who were perhaps the worst of the worst in what was one of the largest empires that ever existed, lasting for over a thousand years.

1. Caligula

Officially known as Gaius (Gaius Caesar Augustus Germanicus), Caligula was the third Roman Emperor, ruling from 37 to 41 AD. He acquired the nickname "Caligula" (meaning "little [soldier's] boot") from his father's soldiers during a campaign.

While recognized for some positive measures in the early days of his rule, he became famous throughout the ages as an absolutely insane emperor, who killed anyone when it pleased him, spent exorbitantly, was obsessed with perverse sex, and proclaimed himself to be a living god.

Caligula gives his horse Incitatus a drink during a banquet. Credit: An engraving by Persichini from a drawing by Pinelli, from "The History of the Roman Emperors" from Augustus to Constantine, by Jean Baptiste Louis Crevier. 1836.

Among his litany of misdeeds, according to the accounts of Caligula's contemporaries Philo of Alexandria and Seneca the Younger, he slept with whomever he wanted, brazenly taking other men's wives (even on their wedding nights) and publicly talking about it.

He also had an insatiable blood thirst, killing for mere amusement. Once, as reports historian Suetonius, when the bridge across the sea at Puteoli was being blessed, he had a number of spectators who were there to inspect it thrown off into the water. When some tried to cling to the ships' rudders, Caligula had them dislodged with hooks and oars so they would drown. On another occasion, he got so bored that he had his guards throw a whole section of the audience into the arena during the intermission so they would be eaten by wild beasts. He also allegedly executed two consuls who forgot his birthday.

Suetonius relayed further atrocities of the mad emperor's character, writing that Caligula "frequently had trials by torture held in his presence while he was eating or otherwise enjoying himself; and kept an expert headsman in readiness to decapitate the prisoners brought in from gaol." One particular form of torture associated with Caligula involved having people sawed in half.

He caused mass starvation and purposefully wasted money and resources, like making his troops stage fake battles just for theater. If that wasn't enough, he turned his palace into a brothel and was accused of incest with his sisters, Agrippina the Younger, Drusilla, and Livilla, whom he also prostituted to other men. Perhaps most famously, he was planning to appoint his favorite horse Incitatus a consul and went as far as making the horse into a priest.

In early 41 AD, Caligula was assassinated by a conspiracy of Praetorian Guard officers, senators, and other members of the court.

2. Nero

Fully named Nero Claudius Caesar, Nero ruled from 54 to 68 AD and was arguably an even worse madman than his uncle Caligula. He had his step-brother Britannicus killed, his wife Octavia executed, and his mother Agrippina stabbed and murdered. He personally kicked to death his lover Poppeaea while she was pregnant with his child — a horrific action the Roman historian Tacitus depicted as "a casual outburst of rage."

He spent exorbitantly and built a 100-foot-tall bronze statue of himself called the Colossus Neronis.

He is also remembered for being strangely obsessed with music. He sang and played the lyre, although it's not likely he really fiddled as Rome burned in what is a popular myth about this crazed tyrant. As misplaced retribution for the fire which burned down a sizable portion of Rome in the year 64, he executed scores of early Christians, some of them outfitted in animal skins and brutalized by dogs, with others burned at the stake.

He died by suicide.

Roman Emperor Nero in the burning ruins of Rome. July 64 AD.Credit: From an original painting by S.J. Ferris. (Photo by Kean Collection / Getty Images)

3. Commodus

Like some of his counterparts, Commodus (a.k.a. Lucius Aelius Aurelius Commodus) thought he was a god — in his case, a reincarnation of the Greek demigod Hercules. Ruling from 176 to 192 AD, he was also known for his debauched ways and strange stunts that seemed designed to affirm his divine status. Numerous statues around the empire showed him as Hercules, a warrior who fought both men and beasts. He fought hundreds of exotic animals in an arena like a gladiator, confusing and terrifying his subjects. Once, he killed 100 lions in a single day.

Emperor Commodus (Joaquin Phoenix) questions the loyalty of his sister Lucilla (Connie Nielsen) In Dreamworks Pictures' and Universal Pictures' Oscar-winning drama "Gladiator," directed by Ridley Scott.Credit: Photo By Getty Images

The burning desire to kill living creatures as a gladiator for the New Year's Day celebrations in 193 AD brought about his demise. After Commodus shot hundreds of animals with arrows and javelins every morning as part of the Plebeian Games leading up to New Year's, his fitness coach (aptly named Narcissus), choked the emperor to death in his bath.

4. Elagabalus

Officially named Marcus Aurelius Antoninus II, Elagabalus's nickname comes from his priesthood in the cult of the Syrian god Elagabal. Ruling as emperor from 218 to 222 AD, he was so devoted to the cult, which he tried to spread in Rome, that he had himself circumcised to prove his dedication. He further offended the religious sensitivities of his compatriots by essentially replacing the main Roman god Jupiter with Elagabal as the chief deity. In another nod to his convictions, he installed on Palatine Hill a cone-like fetish made of black stone as a symbol of the Syrian sun god Sol Invictus Elagabalus.

His sexual proclivities were also not well received at the time. He was likely transgender (wearing makeup and wigs), had five marriages, and was quite open about his male lovers. According to the Roman historian (and the emperor's contemporary) Cassius Dio, Elagabalus prostituted himself in brothels and taverns and was one of the first historical figures on record to be looking for sex reassignment surgery.

He was eventually murdered in 222 in an assassination plot engineered by his own grandmother Julia Maesa.

5. Vitellius

Emperor for just eight months, from April 19th to December 20th of the year 69 AD, Vitellius made some key administrative contributions to the empire but is ultimately remembered as a cruel glutton. He was described by Suetonius as overly fond of eating and drinking, to the point where he would eat at banquets four times a day while sending out the Roman navy to get him rare foods. He also had little social grace, inviting himself over to the houses of different noblemen to eat at their banquets, too.

Vitellius dragged through the streets of Rome.Credit: Georges Rochegrosse. 1883.

He was also quite vicious and reportedly either had his own mother starved to death or approved a poison with which she committed suicide.

Vitellius was ultimately murdered in brutal fashion by supporters of the rival emperor Vespasian, who dragged him through Rome's streets, then likely beheaded him and threw his body into the Tiber river. "Yet I was once your emperor," were supposedly his last words, wrote historian Cassius Dio.

6. Caracalla

Marcus Aurelius Antoninus I ruled Rome from 211 to 217 AD on his own (while previously co-ruling with his father Septimius Severus from 198). "Caracalla"' was his nickname, referencing a hooded coat from Gaul that he brought into Roman fashion.

He started off his rise to individual power by murdering his younger brother Geta, who was named co-heir by their father. Caracalla's bloodthirsty tyranny didn't stop there. He wiped out Geta's supporters and was known to execute any opponents to his or Roman rule. For instance, he slaughtered up to 20,000 citizens of Alexandria after a local theatrical satire dared to mock him.

Geta Dying in His Mother's Arms.Credit: Jacques Pajou (1766-1828)

One of the positive outcomes of his rule was the Edict of Caracalla, which gave Roman citizenship to all free men in the empire. He was also known for building gigantic baths.

Like others on this list, Caracalla met a brutal end, being assassinated by army officers, including the Praetorian prefect Opellius Macrinus, who installed himself as the next emperor.

7. Tiberius

As the second emperor, Tiberius (ruling from 42 BC to 16 AD) is known for a number of accomplishments, especially his military exploits. He was one of the Roman Empire's most successful generals, conquering Pannonia, Dalmatia, Raetia, and parts of Germania.

He was also remembered by his contemporaries as a rather sullen, perverse, and angry man. In the chapter on his life from The Lives of the Twelve Caesars by the historian Suetonius, Tiberius is said to have been disliked from an early age for his personality by even his family. Suetonius wrote that his mother Antonia often called him "an abortion of a man, that had been only begun, but never finished, by nature."

"Orgy of the Times of Tiberius on Capri".Painting by Henryk Siemiradzki. 1881.

Suetonius also paints a damning picture of Tiberius after he retreated from public life to the island of Capri. His years on the island would put Jeffrey Epstein to shame. A horrendous pedophile, Tiberius had a reputation for "depravities that one can hardly bear to tell or be told, let alone believe," Suetonius wrote, describing how "in Capri's woods and groves he arranged a number of nooks of venery where boys and girls got up as Pans and nymphs solicited outside bowers and grottoes: people openly called this 'the old goat's garden,' punning on the island's name."

There's much, much more — far too salacious and, frankly, disgusting to repeat here. For the intrepid or morbidly curious reader, here's a link for more information.

After he died, Tiberius was fittingly succeeded in emperorship by his grandnephew and adopted grandson Caligula.

Physicists push limits of Heisenberg Uncertainty Principle

New studies stretch the boundaries of physics, achieving quantum entanglement in larger systems.

Credit: Aalto University.
Surprising Science
  • New experiments with vibrating drums push the boundaries of quantum mechanics.
  • Two teams of physicists create quantum entanglement in larger systems.
  • Critics question whether the study gets around the famous Heisenberg uncertainty principle.
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The ‘Lost Forty’: how a mapping error preserved an old-growth forest

A 19th-century surveying mistake kept lumberjacks away from what is now Minnesota's largest patch of old-growth trees.

Credit: U.S. Forest Service via Dan Alosso on Substack and licensed under CC-BY-SA
Strange Maps
  • In 1882, Josias R. King made a mess of mapping Coddington Lake, making it larger than it actually is.
  • For decades, Minnesota loggers left the local trees alone, thinking they were under water.
  • Today, the area is one of the last remaining patches of old-growth forest in the state.
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Mixing human + animal DNA and the future of gene editing

"The question is which are okay, which are not okay."

  • As the material that makes all living things what/who we are, DNA is the key to understanding and changing the world. British geneticist Bryan Sykes and Francis Collins (director of the Human Genome Project) explain how, through gene editing, scientists can better treat illnesses, eradicate diseases, and revolutionize personalized medicine.
  • But existing and developing gene editing technologies are not without controversies. A major point of debate deals with the idea that gene editing is overstepping natural and ethical boundaries. Just because they can, does that mean that scientists should be edit DNA?
  • Harvard professor Glenn Cohen introduces another subcategory of gene experiments: mixing human and animal DNA. "The question is which are okay, which are not okay, why can we generate some principles," Cohen says of human-animal chimeras and arguments concerning improving human life versus morality.

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