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National Human Genome Research Institute
March 21, 2017

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National Human Genome Research Institute (NHGRI)

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Fact sheet published by the National Human Genome Research Institute (NHGRI) about cloning (human cloning, animal cloning, therapeutic cloning, etc.)

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Powerful new technique can clone thousands of genes at once

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Powerful new technique can clone thousands of genes at once

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John Hopkins University School of Medicine
6/5/17

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Powerful new technique can clone thousands of genes at once

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Scientists at Johns Hopkins, Rutgers, the University of Trento in Italy, and Harvard Medical School report they have developed a new molecular technique called LASSO cloning, which can be used to isolate thousands of long ...

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NASA

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NASA.gov brings you the latest images, videos and news from America's space agency. Get the latest updates on NASA missions, watch NASA TV live, and learn about our quest to reveal the unknown and benefit all humankind.

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BY Megan Molteni
4/27/18

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In the early days of gene editing, biologists had a molecular tool kit that was somewhat akin to a printing press. Which is to say, altering DNA was a messy, labor-intensive process of loading genes onto viruses bound for target cells. It involved more than a fair amount of finger-crossing. Today, scientists have the genetic equivalent of Microsoft Word, and they are beginning to edit DNA almost as easily as software engineers modify code. The precipitating event? Call it the Great Crispr Quake of 2012.

If you're asking, "what's Crispr?" the short answer is that it's a revolutionary new class of molecular tools that scientists can use to precisely target and cut any kind of genetic material. Crispr systems are the fastest, easiest, and cheapest methods scientists have ever had to manipulate the code of life in any organism on Earth, humans included.

The long answer is that Crispr stands for Clustered Regularly Interspaced Palindromic Repeats. Crispr systems consist of a protein with sequence-snipping capabilities and a genetic GPS guide. Such systems naturally evolved across the bacterial kingdom as a way to remember and defend against invading viruses. But researchers recently discovered they could repurpose that primordial immune system to precisely alter genomes, setting off a billion-dollar boom in DNA hacking.

Every industry is throwing mad money at Crispr-pharma, agriculture, energy, materials manufacturing, you name it. Even the weed guys want in. Companies are using it to make cancer-curing medicines, climate-change-fighting crops, biofuel-oozing algae, and self-terminating mosquitoes. Academic researchers have almost universally adopted Crispr to more deeply understand the biology of their model organisms. Supporting this biohacking bonanza is an increasingly crowded Crispr backend supply chain; businesses building gene-editor design tools and shipping synthetic guide RNAs or pre-Crispr'd cell lines to these companies' doors. So far, though, very few Crispr-enhanced products have made it into the hands of actual consumers. In their place, hyperbolic headlines have bugled society's greatest hopes and fears for the technology, from saving near-extinct species to igniting a superbaby arms race.

Crispr isn't going to end disease or hunger or climate change any time soon. Maybe it never will. Nor is it about to deliver designer children or commit genetic genocide. (Though it's never too early to start talking about the ethical dilemmas such a powerful technology could pose.) Crispr is, however, already beginning to reshape the physical world around us in much less radical ways, one base pair at a time.

The History of Crispr

It all started with yogurt. To make it, dairy producers have long employed the help of Streptococcus thermophilus, a bacteria that gobbles up the lactose in milk and poops out lactic acid. It wasn't until 2005, though, that a young microbiologist named Rodolphe Barrangou discovered that S. thermophilus contained odd chunks of repeating DNA sequences-Crisprs-and that those sequences were keeping it safe from the viruses that attack it and result in spoilage. (If the thermophilus is gone, nastier bacteria can move in and feed off the lactose, ruining the product.)

Before long, DuPont bought the Danish company that Barrangou worked for and began using Crispr to protect all of its yogurt and cheese cultures. Since DuPont owns about 50 percent of the global dairy culture market, that means you've probably already eaten Crispr-optimized cheese on your pizza.

3 (Non-Gene Editing) Uses for Crispr

Diagnose Disease

Viruses work by turning your cells into little factories for their DNA. A Crispr-based test could pick out that foreign DNA from just a drop of blood, spit, or urine and tell you in minutes if you've got the Zika virus, dengue, or yellow fever circulating in your body.

Spot Rot

Every year, fungi wipe out a third of all crops. Crispr panels tuned to identify the worst offenders could help farmers save their harvests before the blight sets in.

Smartbomb Bugs

Thanks to overuse, the world's antibiotic arsenal is losing its effectiveness. New Crispr-based drugs that only target bad bugs would leave your microbiome intact and help fight antibiotic resistance.

All the while, gene sequencing costs were plummeting and research scientists around the world were assembling the genomes of bacteria. As they did, they found Crisprs everywhere-more than half of the bacterial kingdom turned out to have them. Oftentimes those sequences were flanked by a set of genes coding for a class of strand-cutting enzymes called endonucleases. Scientists suspected they were involved in this primitive immune system, but how exactly?

The key insight came from a particularly nasty bug-the one that causes strep throat. Its Crispr system made two RNA sequences that attached to a clam-shaped endonuclease called Cas9. Like a genetic GPS, those sequences directed the enzyme to a strand of DNA complementary to the RNA sequences. When it got there, Cas9 changed shape, grabbing the DNA and slicing it in two. The molecular biologists who made this discovery-Jennifer Doudna and Emmanuelle Charpentier-published their work on bacteria in Science in 2012. But not before patenting the technology as a tool for genetic engineering. If you just switch out the RNA guide, you can send Cas9 anywhere-to the gene that causes Huntington's disease, say, and snip it out. Crispr, they realized, would be a molecular biologist's warp drive.

Six months later, a molecular biologist at the Broad Institute of MIT and Harvard named Feng Zhang published a paper in Science showing how Crispr-Cas9 could edit human cells too. In fact, with the right genetic guides, you can Crispr pretty much anything. That meant it might be put to work on next-generation medicines that could do things like erase genetic defects and supercharge the body's natural defenses against cancer. And that meant big money.

Perhaps predictably, a patent battle ensued- one that is still going on today. Crispr's early pioneers founded three companies with exclusive licenses to exploit Crispr/Cas9 to cure human diseases; the first clinical trials are expected to begin in the US in 2018. Uncertainty over who will ultimately own the technology has done little to slow the appetite for all things Crispr. If anything, it has unleashed a flood of interest in developing competing and adjacent tools that promise to further refine and expand Crispr's already ample potential.

The Future of Crispr

For now, Crispr is still a biologist's buzzword. But just as computers evolved from a nerdy, niche tool for math geeks to a ubiquitous, invisible extension of our own bodies, so Crispr will one day weave seamlessly into the fabric of our physical reality. It will simply be the way to solve a problem, if that problem is remotely biological in nature.

Take industrial fermentation for example. With the help of old-school genetic engineering techniques, scientists have already reprogrammed microbes like E. Coli and brewer's yeast into factories that can make everything from insulin to ethanol. Crispr will rapidly enlarge the catalog of designer chemicals, molecules, and materials that biorefineries can produce. Self-healing concrete? Fire-resistant, plant-based building materials lighter than aluminum? Fully biodegradable plastics? Crispr not only makes all these possible, it makes it possible to produce them at scale.

But we won't get there with the tools we've currently got. Which is why researchers are now racing to chart the full expanses of the Crispr universe. At this moment they're scouring the globe for obscure bacteria to sequence, and they're tinkering with the systems that have already been discovered. They're filing patents on every promising new nuclease they come across, adding to a list that is sure to expand in the coming decade. Each new enzyme will not only advance Crispr's gene editing powers, but extend its capabilities far beyond DNA manipulation. You see, slicing and dicing isn't the only interesting thing to do to DNA. Tricked out new Crispr systems could temporarily toggle genes on and off or surveil the genome to fix mutations as they happen in real time, no snipping required. The first would let scientists treat human diseases where there's too much or too little of a certain substance-say insulin-without permanently altering a patient's DNA. The second could one day prevent diseases like cancer from occurring altogether. The specificity of Crispr, perhaps more than its actual cutting mechanism, will inspire applications we can't yet imagine.

The Amazing Crispr Enzyme Clan

Cas9 | The OG

Good at cutting DNA, great for knockouts. Already being replaced by newer base pair editors with more fine-tuned control.

Cpf1 | The Stickler

Like Cas9 but not as sloppy. It leaves "sticky" DNA ends, which are easier to work with when making edits.

Cas13 | The Cowboy

Cuts RNA not DNA. Could knock down protein levels without permanently changing your genome. Pair it with a reporter signal and you've got a diagnostic.

Cas3 | The Gobbler

Cas3 gives zero f***. It offers no repair mechanism-once it finds that target DNA sequence it just starts cutting till there ain't no DNA left.

CasX/CasY | The X/Y Factor

Just discovered in an abandoned silver mine, we don't know yet what these tiny enzymes' superpowers will be.

Meanwhile, consumers can expect to see their first Crispr'd products lining grocery store shelves very soon. Because Crispr doesn't use plant viruses to manipulate DNA (the old GMO-generating method), the USDA has given a free regulatory pass to gene-edited crops, allowing drought-tolerant soybeans and extra-starchy corn to ease into your favorite processed foods. Specialty fruits and vegetables will likely follow the commodity crops; the reduced regulatory burden and the cheapness of Crispr will allow companies appealing to consumers' senses rather than farmers' bottom lines to enter the market. Already a dozen or so startups have popped up to challenge the Bayer/Monsanto, DowDupont/Pioneers of the world.

This democratizing aspect of Crispr-based tech, combined with its nearly limitless commercial possibilities, make today a great time to be a molecular biologist. Want to make antibiotics that only target bad bugs without wiping out the entire microbiome? There are companies doing that. Want to make paper-based diagnostics that doctors can take into the field to test for diseases like dengue and Zika? There are research labs and startups doing that too. And as more tools come online, the backend Crispr ecosystem will continually expand to support, supply, and optimize them.

Crispr applications are only going to become more powerful, and when they do they will rightly invite more scrutiny, and probably more regulation. We're going to have to figure out if it's OK to wipe out an entire species in the name of conservation and bring other ones back from extinction. We'll have to wrestle with the possibility that gene editing tools might be used to produce biological weapons of unfathomable destruction. And yes, we'll eventually have to talk about designer babies; when is it acceptable to fix a genetic mutation? Would we ever start adding features? Where do we draw the line? Crispr, and all the tools that will one day make up the Crispr universe will undoubtedly force societies-not just scientists-to confront these questions and ponder the oldest one of all; what does it mean to be human?

Learn More:

Everything You Need To Know About Crispr Gene Editing
Okay, you get it, Crispr's a big deal. But now, aren't you curious to know exactly how it works? You don't have to be a microbiologist to understand this step-by-step look inside the molecular multitool of the century.

Read This Before You Freak Out Over Gene-Edited Superbabies
In the last few years, scientists in the US and China have used Crispr to fix genetic mutations in human embryos, prompting concerns over the imminent takeover of genetically superior designer children. Breathe, people: You don't need to worry about that for a long, long, long time.

Plus! Crispr uploads a galloping horse GIF into a living bacteria and more WIRED gene editing coverage.
This guide was last updated on April 26, 2018. Enjoyed this deep dive? Check out more WIRED Guides.

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Everything You Need To Know About Crispr Gene Editing

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In the early days of gene editing, biologists had a molecular tool kit that was somewhat akin to a printing press. Which is to say, altering DNA was a messy, labor-intensive process of loading genes onto viruses bound for target cells. It involved more than a fair amount of finger-crossing.

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4/20/18

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CRISPR is a powerful tool for editing genomes, meaning it allows researchers to easily alter DNA sequences and modify gene function. It has many potential applications, including correcting genetic defects, treating and preventing the spread of diseases, and improving the growth and resilience of crops. However, despite its promise, the technology also raises ethical concerns.

In popular usage, "CRISPR" (pronounced "crisper") is shorthand for "CRISPR-Cas9." CRISPRs are specialized stretches of , and the protein Cas9 - where Cas stands for "CRISPR-associated" - is an that acts like a pair of molecular scissors, capable of cutting strands of DNA.

CRISPR technology was adapted from the natural defense mechanisms of and archaea, a domain of relatively simple single-celled microorganisms. These organisms use CRISPR-derived , a molecular cousin to DNA, and various Cas proteins to foil attacks by . To foil attacks, the organisms chop up the DNA of viruses and then stow bits of that DNA in their own genome, to be used as a weapon against the foreign invaders should those viruses attack again.

When the components of CRISPR are transferred into other, more complex, organisms, those components can then manipulate genes, a process called "gene editing." No one really knew what this process looked like until 2017, when a team of researchers led by Mikihiro Shibata of Kanazawa University in Japan and Hiroshi Nishimasu of the University of Tokyo showed, for the very first time, what it looks like when a CRISPR is in action, Live Science previously reported.

Related: Genetics by the numbers: 10 tantalizing tales

Key components of CRISPR

CRISPRs: The term "CRISPR" stands for "clusters of regularly interspaced short palindromic repeats" and describes a region of DNA made up of short, repeated sequences with so-called "spacers" sandwiched between each repeat.

When we talk about repeats in the genetic code, we're talking about the ordering of rungs within the spiral ladder of a DNA molecule. Each rung contains two chemical bases bound together: A base called adenine (A) links up to another called thymine (T), and the base guanine (G) pairs with cytosine (C).

In a CRISPR region, these bases appear in the same order several times, and in these repeated segments, they form what's known as "palindromic" sequences, according to the Max Planck Institute. A palindrome, like the word "racecar," reads the same forward as it does backward; similarly, in a palindromic sequence, bases on one side of the DNA ladder match those on the opposing side when you read them in opposite directions.

For example, a super simple palindromic sequence might look like this:

Short palindromic repeats appear throughout CRISPR regions of DNA, with each repeat bookended by "spacers." Bacteria swipe such spacers from viruses that have attacked them, meaning they incorporate a bit of viral DNA into their own genome. These spacers serve as a bank of memories, which enables the bacteria to recognize the viruses if they should ever attack again. You can also think of spacers like "Wanted" posters, providing a snapshot of the bad guys so they can be easily spotted and brought to justice.

Related: Going viral: 6 new findings about viruses

Rodolphe Barrangou and a team of researchers at Danisco, a food ingredients company, first demonstrated this process experimentally. In a 2007 paper published in the journal Science, the researchers used Streptococcus thermophilus bacteria, which are commonly found in yogurt and other dairy cultures, as their model, according to the Joint Genome Institute, part of the U.S. Department of Energy. They observed that after a viral attack, the bacteria incorporated new spacers into their CRISPR regions. Moreover, the DNA sequence of these spacers was identical to parts of the virus genome.

The team also manipulated the spacers by removing them and inserting new viral DNA sequences in their place. In this way, the researchers were able to alter the bacteria's resistance to an attack by a specific virus, confirming CRISPRs' role in regulating bacterial immunity.

CRISPR RNA (crRNA): CRISPR regions of DNA act as a kind of bank of viral memories; but for that stored information to be useful elsewhere in the cell, it must be copied, or "transcribed," into a different genetic molecule called RNA. Unlike DNA sequences, which remain lodged inside the DNA molecule, this CRISPR RNA (crRNA) can roam about the cell and team up with proteins - namely the molecular scissors that snip viruses to bits.

RNA also differs from DNA in that it's only one strand, rather than two, meaning it looks like just a half of a ladder. To build an RNA molecule, one part of the CRISPR acts as a template and proteins called polymerases swoop in to construct an RNA molecule that is "complementary" to that template, meaning the two strands' bases would fit together like puzzle pieces. For example, a G in the DNA molecule would get transcribed as a C in the RNA.

Each snippet of CRISPR RNA contains a copy of a repeat and a spacer from a CRISPR region of DNA, according to a 2014 review by Jennifer Doudna and Emmanuelle Charpentier, published in the journal Science. The crRNA interacts with the Cas9 protein and another kind of RNA, called "trans-activating crRNA" or tracrRNA, in order to help bacteria fend off viruses.

Cas9: The Cas9 protein is an enzyme that cuts foreign DNA. The protein binds to crRNA and tracrRNA, which together guide Cas9 to a target site on the virus's DNA strand where the protein will make its cut. The target DNA that the Cas9 will cut through is complementary to a 20-nucleotide stretch of the crRNA, where a "nucleotide" is a building block of DNA that contains one base.

Using two separate regions or "domains" on its structure, Cas9 cuts both strands of the DNA double helix, making what is known as a "double-stranded break," according to the 2014 Science article.

There is a built-in safety mechanism that ensures that Cas9 doesn't just cut just anywhere in a genome. Short DNA sequences known as "protospacer adjacent motifs," or PAMs, serve as tags and sit adjacent to the target DNA sequence. If the Cas9 complex doesn't see a PAM next to its target DNA sequence, it won't cut. This is one possible reason that Cas9 doesn't ever attack the CRISPR region in bacteria, according to a 2014 review published in Nature Biotechnology.

How CRISPR works as a genome-editing tool

Genomes encode a series of messages and instructions within their DNA sequences, and genome editing involves changing those sequences, thereby changing the messages they contain. This can be done by inserting a cut or break in the DNA and tricking a cell's natural DNA repair mechanisms into introducing the targeted changes. CRISPR-Cas9 provides a means to do so.

In 2012, two pivotal research papers were published in the journals Science and , describing how the bacterial CRISPR-Cas9 could be used to chop up any DNA, not just that of viruses. In this way, the natural CRISPR system could be transformed into a simple, programmable genome-editing tool.

To direct Cas9 to snip a specific region of DNA, scientists can simply change the sequence of the crRNA, which binds to a complementary sequence in the target DNA, the studies concluded.In the 2012 Science article, Martin Jinek and his colleagues further simplified the system by fusing crRNA and tracrRNA to create a single "guide RNA." Thus, genome editing requires only two components: a guide RNA and the Cas9 protein.

"Operationally, you design a stretch of 20 base pairs that match a gene that you want to edit," and from there, one can figure out what the complementary crRNA sequence would be, George Church, a professor of genetics at Harvard Medical School, told Live Science. Church emphasized the importance of making sure that the nucleotide sequence is found only in the target gene and nowhere else in the genome.

"Then the RNA plus the protein [Cas9] will cut - like a pair of scissors - the DNA at that site, and ideally nowhere else," Church explained. Once the DNA is cut, the cell's natural repair mechanisms kick in and work to piece the DNA back together, and at this point, edits can be made to the genome. There are two ways this can happen:

According to the Huntington's Outreach Project at Stanford University, one repair method involves gluing the two cuts back together. This method, known as "non-homologous end joining," tends to introduce errors where nucleotides are accidentally inserted or deleted, resulting in that could disrupt a gene.

In the second method, the break is fixed by filling in the gap with a sequence of nucleotides. In order to do so, the cell uses a short strand of DNA as a template. Scientists can supply the DNA template of their choosing, thereby writing-in any gene they want, or correcting a mutation.

Who discovered CRISPR?

Scientists originally discovered the CRISPRs in bacteria in 1987, but they didn't initially understand the biological significance of the DNA sequences, and they didn't yet call them "CRISPRs," according to Quanta Magazine. Yoshizumi Ishino and colleagues at Osaka University in Japan first found the characteristic nucleotide repeats and spacers in the gut microbe , and as the technology for genetic analysis improved in the 1990s, other researchers found CRISPRs in many other microbes.

Francisco Mojica, a scientist at the University of Alicante in Spain, was the first to describe the distinct characteristics of CRISPRs and found the sequences in 20 different microbes, according to a 2016 report in the journal Cell. At one point, he dubbed the sequences "short regularly spaced repeats" (SRSRs), but he later suggested that they be called CRISPRs instead. The term CRISPR first appeared in a 2002 report, published in the journal Molecular Microbiology and authored by Ruud Jansen of Utrecht University, with whom Mojica had been in correspondence.

In the following years, scientists also discovered Cas genes and the function of Cas enzymes, and they figured out that the spacers in CRISPRs came from invasive viruses, Quanta reported.

Among these pioneering researchers was Jennifer Doudna, a professor of biochemistry, biophysics and structural biology at the University of California, Berkeley, who went on to share the 2020 Nobel Prize in chemistry with Emmanuelle Charpentier, director of the Max Planck Unit for the Science of Pathogens. The two scientists are credited with adapting the bacterial CRISPR/Cas system into a handy gene-editing tool, Live Science previously reported.

Charpentier initially discovered tracrRNA while studying the bacteria Streptococcus pyogenes, which causes a range of diseases from tonsillitis to sepsis. Having uncovered tracrRNA as a previously unknown component of the CRISPR/Cas system, Charpentier began collaborating with Doudna to recreate that system in a test tube. In 2012, the team published their seminal work in the journal Science, announcing that they'd successfully simplified the molecular scissors into a gene-editing tool.

Some thought that biochemist Feng Zhang of the Broad Institute might also earn the Nobel for his own, separate work with the CRISPR system, Science Magazine reported. Zhang demonstrated that the CRISPR system works in mammalian cells, and based on this work, the Broad Institute earned the first patent for the use of CRISPR gene-editing technology in eukaryotes, or complex cells with nuclei to hold their DNA.

How has CRISPR been used?

(Image credit: KEITH CHAMBERS/SCIENCE PHOTO LIBRARY via Getty Images)

In 2013, researchers in the labs of Church and Zhang published the first reports describing the use of CRISPR-Cas9 to edit human cells in an experimental setting. Studies conducted in lab dish and animal models of human disease have demonstrated that the technology can effectively correct genetic defects. Examples of such diseases include cystic fibrosis, cataracts and Fanconi anemia, according to a 2016 review article published in the journal Nature Biotechnology. These studies have paved the way for therapeutic applications in humans.

In the realm of medicine, CRISPR has been tested in early-stage clinical trials as cancer therapy and as a treatment for an inherited disorder that causes blindness. It's also been investigated as a strategy for preventing the spread of Lyme disease and malaria from viral vectors to people, and it's also been studied in animal models of HIV as a way to rid infected cells of the virus, Live Science previously reported. One research team in China attempted to treat a human patient's HIV using CRISPR, and while the treatment wasn't successful in curing the infection, the gene therapy also didn't cause any harmful effects, Live Science reported.

"I think the public perception of CRISPR is very focused on the idea of using gene editing clinically to cure disease," said Neville Sanjana of the New York Genome Center and an assistant professor of biology, neuroscience and physiology at New York University. "This is no doubt an exciting possibility, but this is only one small piece."
Related: 10 amazing things scientists just did with CRISPR
CRISPR technology has also been applied in the food and agricultural industries to engineer probiotic cultures and to vaccinate industrial cultures (yogurt, for example) against viruses. It is also being used in crops to improve yield, drought tolerance and nutritional properties.

One other potential application is to create gene drives, a genetic engineering technique that increases the chances of a particular trait passing on from parent to offspring; this kind of genetic engineering derives from a natural phenomenon, where specific versions of genes are more likely to be inherited. Eventually, over the course of generations, the trait spreads through entire populations, according to the Wyss Institute. Gene drives could be used for various applications, such as eradicating invasive species or reversing pesticide and herbicide resistance in crops, according to a 2014 report published in the journal .

During the COVID-19 pandemic, the CRISPR-Cas9 system has been used to develop various diagnostic tests for the viral infection, BBC News reported.

In April 2017, a team of researchers released research in the journal Science that they had programmed a CRISPR molecule to find strains of viruses, such as Zika, in blood serum, urine and saliva.

On Aug. 2, 2017, scientists revealed in the journal Nature that they had removed a heart disease defect in an embryo successfully using CRISPR.

On Jan. 2, 2018, researchers announced that they may be able to stop fungi and other problems that threaten chocolate production using CRISPR to make the plants more resistant to disease.

On April 16, 2018, researchers upgraded CRISPR to edit thousands of genes at once, according to research published by the journal BioNews.

In addition, CRISPR has recently been used in the following ways:

However, despite its wide range of uses, the tool is not without its drawbacks.

"I think the biggest limitation of CRISPR is it is not a hundred percent efficient," Church told Live Science. That means, in a given experiment, CRISPR may successfully edit only a percentage of the targeted DNA. According to the 2014 Science article by Doudna and Charpentier, in a study conducted in rice, gene editing occurred in nearly 50% of the cells that received the Cas9-RNA complex. Meanwhile, other analyses have shown that depending on the target, editing efficiencies can reach as high as 80% or more.

The technology can also create "off-target effects" when DNA is cut at sites other than the intended target. This can lead to the introduction of unintended mutations. Furthermore, Church noted, even when the system cuts on target, there is a chance of not getting a precise edit. He called this "genome vandalism."

Potential risks and ethical concerns of using CRISPR

The many potential applications of CRISPR technology raise questions about the ethical merits and consequences of tampering with genomes. And in particular, a slew of ethical debates flared up in 2018 when He Jiankui, formerly a biophysicist at the Southern University of Science and Technology in Shenzhen, announced that his team had edited DNA in human embryos and thus created the world's first gene-edited babies.

He was subsequently sentenced to three years in prison and fined 3 million yuan ($560,000) for practicing medicine without a license, violating Chinese regulations on human-assisted reproductive technology and fabricating ethical review documents, Live Science previously reported. But even after his sentencing, He's experiments raised questions about how the use of CRISPR should be regulated going forward, especially given that the technology is still fairly new.

Illegal experimentation in human embryos represents an extreme misuse of CRISPR, of course, but even seemingly ethical uses of the technology could carry risks, scientists say.

In general, making genetic modifications to human embryos and reproductive cells such as sperm and eggs is known as germline editing. Since changes to these cells can be passed on to subsequent generations, using CRISPR technology to make germline edits has raised a number of ethical concerns.

Variable efficacy, off-target effects and imprecise edits all pose safety risks. In addition, there is much that is still unknown to the scientific community. In a 2015 article published in Science, David Baltimore and a group of scientists, ethicists and legal experts note that germline editing raises the possibility of unintended consequences for future generations "because there are limits to our knowledge of human genetics, gene-environment interactions, and the pathways of disease (including the interplay between one disease and other conditions or diseases in the same patient)."

In the 2014 Science article, Oye and colleagues point to the potential ecological impact of using gene drives. An introduced trait could spread beyond the target population to other organisms through crossbreeding. Gene drives could also reduce the genetic diversity of the target population, potentially hampering its ability to survive.

Other ethical concerns are more nuanced. Should we make changes that could fundamentally affect future generations without having their consent? What if the use of germline editing veers from being a therapeutic tool to an enhancement tool for various human characteristics?

To address these concerns, the National Academies of Sciences, Engineering and Medicine put together a comprehensive report with guidelines and recommendations for genome editing.

Although the National Academies urge caution in pursuing germline editing, they emphasize "caution does not mean prohibition." They recommend that germline editing be done only on genes that lead to serious diseases and only when there are no other reasonable treatment alternatives. Among other criteria, they stress the need to collect data on the health risks and benefits and to maintain continuous oversight during clinical trials. They also recommend that, after a trial concludes, trial organizers should follow up with the participants' families for multiple generations to see what changes persist in the genome over time.
This article includes additional reporting by Alina Bradford, Live Science contributor. Originally published on Live Science.
Additional resources

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CRISPR is a powerful tool for editing genomes, meaning it allows researchers to easily alter DNA sequences and modify gene function. It has many potential applications, including correcting genetic defects, treating and preventing the spread of diseases, and improving the growth and resilience of crops. However, despite its promise, the technology also raises ethical concerns.

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Opinion: Should we use gene editing to produce disease-free babies? A scientist who helped discover CRISPR weighs in.

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Opinion: Should we use gene editing to produce disease-free babies? A scientist who helped discover CRISPR weighs in.

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Jennifer A. Doudna and Samuel H. Sternberg

08/22/17

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Researchers recently reported that they were able to edit human embryos to fix a dangerous mutation. The technology is inching closer to reality, so we need to take a stand, says biochemist Jennifer Doudna.

If CRISPR can help parents conceive a disease-free child when no other options exist and it can do so safely, ought we to use it? It's a question I've asked myself again and again - and one that is particularly timely due to the Nature study published this month that described how scientists at Oregon Health and Science University, working with collaborators in California, China and South Korea, were able to correct human embryos of a common and harmful genetic mutation.

Unsurprisingly, Americans are having a hard time agreeing on an answer: a 2016 Pew Research poll found that 50 percent of adults in the US oppose the idea of reducing the risk of disease using germline editing, compared to 48 percent in favor. (When it comes to making nonessential enhancements to a baby's genome, we seem to be considerably more unified; only 15 percent of the poll's respondents were in favor.)

Religion is one obvious moral compass that people use to confront difficult questions like this, though perspectives can vary widely. When it comes to experimentation with human embryos, some Christian communities are opposed because they regard the embryo as a person from conception, whereas Jewish and Muslim traditions tend to be more accepting because they do not consider embryos created in vitro to be people. And while some religions see any interventions in the germline as a usurpation of God's role in humanity, others welcome human involvement in nature as long as the goals pursued are inherently good.

Humans have been reproducing for millennia aided only by the DNA mutations that arise naturally, and for us to begin directing that process ​seems almost perverse.

Yet another moral guidepost is purely internal: the visceral, knee-jerk reaction to the idea of using CRISPR to permanently edit a future child's genes. For many people, the very idea feels unnatural and wrong, and I was one of those people when I first started thinking about the issue. Humans have been reproducing for millennia aided only by the DNA mutations that arise naturally, and for us to begin directing the process ​- ​similar to the way that plant biologists might genetically modify corn ​- ​seems almost perverse at first glance. As National Institutes of Health director Francis Collins put it, "Evolution has been working toward optimizing the human genome for 3.85 billion years. Do we really think that some small group of human genome tinkerers could do better without all sorts of unintended consequences?"

While I share the general feeling of unease at the idea of humans taking control of their evolution, I wouldn't go so far as to say that nature has fine-tuned our genetic composition. Obviously, evolution didn't optimize the human genome for the present era, when modern foods, computers and high-speed transportation have completely transformed the way we live. And if we look over our shoulders at the course of evolution that has led to this moment, we'll see it's littered with organisms that didn't benefit from the mutational chaos that underpins evolution. Nature is less an engineer than a tinkerer - and a fairly sloppy one at that. Its carelessness can seem like outright cruelty for those people who have inherited genetic mutations that turned out to be suboptimal.

Similarly, the argument that germline editing is unnatural doesn't carry much weight with me anymore. When it comes to human affairs and especially the world of medicine, the line between natural and unnatural blurs to the point of disappearing. We wouldn't call a coral reef unnatural, but we might use the term for a megalopolis like Tokyo. Is this because one is crafted by humans and the other isn't? In my mind, the distinction between natural and unnatural is a false dichotomy, and if it prevents us from alleviating human suffering, it's also a dangerous one.

One woman told me: "If I could use germline editing to remove this mutation from the human population so that no one else suffers as my sister did, I would do it in a heartbeat!"

I've had numerous opportunities to meet with people who have experienced genetic disease themselves or in their families, and their stories are deeply moving. One woman pulled me aside at a conference to share her personal story after a session in which I had discussed CRISPR technology. Her sister had suffered from a rare but devastating genetic disease that affected her physical and mental health and caused tremendous hardship for the entire family. "If I could use germline editing to remove this mutation from the human population so that no one else suffers as my sister did, I would do it in a heartbeat!" she said, tears welling up in her eyes.

On another occasion, a man came to visit me and explained that his father and grandfather had died of Huntington's disease and that three of his sisters had tested positive for the trait. He wanted to do anything he could to advance research toward a cure or, better yet, prevention of this terrible disease. I did not have the heart to ask him if he carried the mutated gene. If he did, he could expect to be robbed of his powers of movement and speech before much longer and to meet an early death ​- ​a terrible sentence for anyone to see placed on their loved ones, let alone be subjected to themselves. Stories like these underscore the terrible human costs of genetic diseases. If we have tools that can one day help doctors safely and effectively correct mutations, whether prior to or just after conception, it seems to me that we'd be justified in using them.

It's not a stretch to think that wealthy families would benefit from germline editing more than others, at least in the beginning.

Setting aside the inherent rightness or wrongness of editing the germline, another ethical issue continues to nag at me: how would CRISPR affect society? Just as it's hard to know where we'd draw the line when it comes to editing embryos, it's difficult to see how we'd do it equitably ​- ​that is, in a way that improves human health across the board, not just in certain groups. It's not a stretch to think that wealthy families would benefit from germline editing more than others, at least in the beginning. Recent gene therapies have hit the market with a price tag of around a million dollars, and it's likely the first gene-editing therapies will be no different.

Of course, new technologies shouldn't be rejected simply because they're expensive. You need look no further than personal computers, cell phones, and direct-to-consumer DNA sequencing to see how costs of new technologies generally diminish over time as improvements are made, leading to a resulting increase in access. Furthermore, there's also the chance that germline editing, like other medical treatments, could one day be subsidized by health insurance.

This might certainly seem like only a remote possibility in the US, since existing reproductive procedures such as IVF and PGD, which routinely cost tens of thousands of dollars, are seldom covered by insurance. But in France, Israel, Sweden and other countries whose national health plans cover assisted reproduction, it's possible that simple economics will incentivize governments to make gene editing available to patients who need it. After all, providing lifelong treatment to a single person with a genetic disease could be much more expensive than intervention in the embryo using gene editing.

But even in countries with comprehensive health-care systems where people from all classes could benefit from germline editing, there's a risk that it might give rise to genetic inequalities, creating a new "gene gap" that would only widen over time. Since the wealthy would be able to afford the procedure more often and since any beneficial genetic modifications made to an embryo would be transmitted to that person's offspring, linkages between class and genetics would ineluctably grow from one generation to the next, no matter how small the disparity in access might be.

Consider the effect this could have on the socioeconomic fabric of society - if you think our world is unequal now, just imagine it stratified along socioeconomic and genetic lines. Envision a future where people with more money live healthier and longer lives, thanks to their privileged sets of genes. It's the stuff of science fiction, but if germline editing becomes routine, this fiction could become reality.

Using gene editing to "fix" things like deafness or obesity could create a less inclusive society, one that pressures everyone to be the same.  ​

Germline editing may also create a different kind of injustice. As disability-rights advocates have pointed out, using gene editing to "fix" things like deafness or obesity could create a less inclusive society, one that pressures everyone to be the same ​- ​and perhaps even encourages more discrimination against differently abled people ​- ​instead of celebrating our natural differences. After all, the human genome is not mere software with bugs that we should categorically eliminate. Part of what makes our species unique and our society so strong is its diversity. While some disease-causing gene mutations produce defective or abnormal proteins on a biochemical level, the individuals who live with the disease are certainly not defective or abnormal people, and they might live happy lives and not feel any need for gene repair.

This fear ​- ​that gene editing will exacerbate existing prejudices against people who fall outside a narrow range of genetic norms ​- ​underlies the association that numerous writers have made between germline editing and eugenics. That concept is best known today for its popularity in Nazi Germany, where a quest to perfect the human race reached its terrible zenith through the forced sterilization of hundreds of thousands of people and the widespread extermination of millions of Jews, homosexuals, the mentally ill and others deemed unworthy of life.

Eugenics as practiced by the Nazis was utterly reprehensible, but I believe the odds are minuscule we'll see anything similar happen with gene editing. Governments are simply not going to begin forcing parents to edit their children's genes. (In fact, the procedure is still illegal in many places.) Unless we're talking about coercive regimes controlling their citizens' procreative liberty, germline editing would remain a private decision for individual parents to make for their own children, not a decision for bureaucrats to make for the population at large.

My views on the ethics of germline editing continue to evolve, ​but as they do, I find myself returning time and again to the issue of choice. Above all else, we must respect people's freedom to choose their own genetic destiny and strive for healthier, happier lives. If people are given this freedom, they will do with it what they personally think is right, ​whatever that may be. As Charles Sabine, a victim of Huntington's disease, put it, "Anyone who has to actually face the reality of one of these diseases is not going to have a remote compunction about thinking that there is any moral issue at all." Who are we to tell him otherwise?
Excerpted from the new book A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution by Jennifer A. Doudna and Samuel H. Sternberg. Copyright © 2017 Jennifer A. Doudna and Samuel H. Sternberg. Reprinted by permission of Houghton Mifflin Harcourt. All rights reserved.

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Opinion: Should we use gene editing to produce disease-free babies? A scientist who helped discover CRISPR weighs in.

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Researchers recently reported that they were able to edit human embryos to fix a dangerous mutation. The technology is inching closer to reality, so we need to take a stand, says biochemist Jennife...

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Heidi Ledford
6/03/15

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Three years ago, Bruce Conklin came across a method that made him change the course of his lab.

Conklin, a geneticist at the Gladstone Institutes in San Francisco, California, had been trying to work out how variations in DNA affect various human diseases, but his tools were cumbersome. When he worked with cells from patients, it was hard to know which sequences were important for disease and which were just background noise. And engineering a mutation into cells was expensive and laborious work. "It was a student's entire thesis to change one gene," he says.

Then, in 2012, he read about a newly published technique called CRISPR that would allow researchers to quickly change the DNA of nearly any organism - including humans. Soon after, Conklin abandoned his previous approach to modelling disease and adopted this new one. His lab is now feverishly altering genes associated with various heart conditions. "CRISPR is turning everything on its head," he says.

The sentiment is widely shared: CRISPR is causing a major upheaval in biomedical research. Unlike other gene-editing methods, it is cheap, quick and easy to use, and it has swept through labs around the world as a result. Researchers hope to use it to adjust human genes to eliminate diseases, create hardier plants, wipe out pathogens and much more besides. "I've seen two huge developments since I've been in science: CRISPR and PCR," says John Schimenti, a geneticist at Cornell University in Ithaca, New York. Like PCR, the gene-amplification method that revolutionized genetic engineering after its invention in 1985, "CRISPR is impacting the life sciences in so many ways," he says.

But although CRISPR has much to offer, some scientists are worried that the field's breakneck pace leaves little time for addressing the ethical and safety concerns such experiments can raise. The problem was thrust into the spotlight in April, when news broke that scientists had used CRISPR to engineer human embryos (see Nature 520, 593-595; 2015). The embryos they used were unable to result in a live birth, but the report has generated heated debate over whether and how CRISPR should be used to make heritable changes to the human genome. And there are other concerns. Some scientists want to see more studies that probe whether the technique generates stray and potentially risky genome edits; others worry that edited organisms could disrupt entire ecosystems.

"This power is so easily accessible by labs - you don't need a very expensive piece of equipment and people don't need to get many years of training to do this," says Stanley Qi, a systems biologist at Stanford University in California. "We should think carefully about how we are going to use that power."

Research revolution

Biologists have long been able to edit genomes with molecular tools. About ten years ago, they became excited by enzymes called zinc finger nucleases that promised to do this accurately and efficiently. But zinc fingers, which cost US$5,000 or more to order, were not widely adopted because they are difficult to engineer and expensive, says James Haber, a molecular biologist at Brandeis University in Waltham, Massachusetts. CRISPR works differently: it relies on an enzyme called Cas9 that uses a guide RNA molecule to home in on its target DNA, then edits the DNA to disrupt genes or insert desired sequences. Researchers often need to order only the RNA fragment; the other components can be bought off the shelf. Total cost: as little as $30. "That effectively democratized the technology so that everyone is using it," says Haber. "It's a huge revolution."

CRISPR methodology is quickly eclipsing zinc finger nucleases and other editing tools (see 'The rise of CRISPR'). For some, that means abandoning techniques they had taken years to perfect. "I'm depressed," says Bill Skarnes, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, "but I'm also excited." Skarnes had spent much of his career using a technology introduced in the mid-1980s: inserting DNA into embryonic stem cells and then using those cells to generate genetically modified mice. The technique became a laboratory workhorse, but it was also time-consuming and costly. CRISPR takes a fraction of the time, and Skarnes adopted the technique two years ago.

Researchers have traditionally relied heavily on model organisms such as mice and fruit flies, partly because they were the only species that came with a good tool kit for genetic manipulation. Now CRISPR is making it possible to edit genes in many more organisms. In April, for example, researchers at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, reported using CRISPR to study Candida albicans, a fungus that is particularly deadly in people with weakened immune systems, but had been difficult to genetically manipulate in the lab. Jennifer Doudna, a CRISPR pioneer at the University of California, Berkeley, is keeping a list of CRISPR-altered creatures. So far, she has three dozen entries, including disease-causing parasites called trypanosomes and yeasts used to make biofuels.

Yet the rapid progress has its drawbacks. "People just don't have the time to characterize some of the very basic parameters of the system," says Bo Huang, a biophysicist at the University of California, San Francisco. "There is a mentality that as long as it works, we don't have to understand how or why it works." That means that researchers occasionally run up against glitches. Huang and his lab struggled for two months to adapt CRISPR for use in imaging studies. He suspects that the delay would have been shorter had more been known about how to optimize the design of guide RNAs, a basic but important nuance.

By and large, researchers see these gaps as a minor price to pay for a powerful technique. But Doudna has begun to have more serious concerns about safety. Her worries began at a meeting in 2014, when she saw a postdoc present work in which a virus was engineered to carry the CRISPR components into mice. The mice breathed in the virus, allowing the CRISPR system to engineer mutations and create a model for human lung cancer. Doudna got a chill; a minor mistake in the design of the guide RNA could result in a CRISPR that worked in human lungs as well. "It seemed incredibly scary that you might have students who were working with such a thing," she says. "It's important for people to appreciate what this technology can do."

Andrea Ventura, a cancer researcher at Memorial Sloan Kettering Cancer Center in New York and a lead author of the work, says that his lab carefully considered the safety implications: the guide sequences were designed to target genome regions that were unique to mice, and the virus was disabled such that it could not replicate. He agrees that it is important to anticipate even remote risks. "The guides are not designed to cut the human genome, but you never know," he says. "It's not very likely, but it still needs to be considered."

Editing out disease

Last year, bioengineer Daniel Anderson of the Massachusetts Institute of Technology in Cambridge and his colleagues used CRISPR in mice to correct a mutation associated with a human metabolic disease called tyrosinaemia. It was the first use of CRISPR to fix a disease-causing mutation in an adult animal - and an important step towards using the technology for gene therapy in humans (see 'A brief history of CRISPR').

The idea that CRISPR could accelerate the gene-therapy field is a major source of excitement in scientific and biotechnology circles. But as well as highlighting the potential, Anderson's study showed how far there is to go. To deliver the Cas9 enzyme and its guide RNA into the target organ, the liver, the team had to pump large volumes of liquid into blood vessels - something that is not generally considered feasible in people. And the experiments corrected the disease-causing mutation in just 0.4% of the cells, which is not enough to have an impact on many diseases.

Over the past two years, a handful of companies have sprung up to develop CRISPR-based gene therapy, and Anderson and others say that the first clinical trials of such a treatment could happen in the next one or two years. Those first trials will probably be scenarios in which the CRISPR components can be injected directly into tissues, such as those in the eye, or in which cells can be removed from the body, engineered in the lab and then put back. For example, blood-forming stem cells might be corrected to treat conditions such as sickle-cell disease or β-thalassaemia. It will be a bigger challenge to deliver the enzyme and guide RNA into many other tissues, but researchers hope that the technique could one day be used to tackle a wider range of genetic diseases.

Yet many scientists caution that there is much to do before CRISPR can be deployed safely and efficiently. Scientists need to increase the efficiency of editing, but at the same time make sure that they do not introduce changes elsewhere in the genome that have consequences for health. "These enzymes will cut in places other than the places you have designed them to cut, and that has lots of implications," says Haber. "If you're going to replace somebody's sickle-cell gene in a stem cell, you're going to be asked, 'Well, what other damage might you have done at other sites in the genome?'"

Keith Joung, who studies gene editing at Massachusetts General Hospital in Boston, has been developing methods to hunt down Cas9's off-target cuts. He says that the frequency of such cuts varies widely from cell to cell and from one sequence to another: his lab and others have seen off-target sites with mutation frequencies ranging from 0.1% to more than 60%. Even low-frequency events could potentially be dangerous if they accelerate a cell's growth and lead to cancer, he says.

With so many unanswered questions, it is important to keep expectations of CRISPR under control, says Katrine Bosley, chief executive of Editas, a company in Cambridge, Massachusetts, that is pursuing CRISPR-mediated gene therapy. Bosley is a veteran of commercializing new technologies, and says that usually the hard part is convincing others that an approach will work. "With CRISPR it's almost the opposite," she says. "There's so much excitement and support, but we have to be realistic about what it takes to get there."

CRISPR on the farm

While Anderson and others are aiming to modify DNA in human cells, others are targeting crops and livestock. Before the arrival of gene-editing techniques, this was generally done by inserting a gene into the genome at random positions, along with sequences from bacteria, viruses or other species that drive expression of the gene. But the process is inefficient, and it has always been fodder for critics who dislike the mixing of DNA from different species or worry that the insertion could interrupt other genes. What is more, getting genetically modified crops approved for use is so complex and expensive that most of those that have been modified are large commodity crops such as maize (corn) and soya beans.

With CRISPR, the situation could change: the ease and low cost may make genome editing a viable option for smaller, speciality crops, as well as animals. In the past few years, researchers have used the method to engineer petite pigs and to make disease-resistant wheat and rice. They have also made progress towards engineering dehorned cattle, disease-resistant goats and vitamin-enriched sweet oranges. Doudna anticipates that her list of CRISPR-modified organisms will grow. "There's an interesting opportunity to consider doing experiments or engineering pathways in plants that are not as important commercially but are very interesting from a research perspective - or for home vegetable gardens," she says.

CRISPR's ability to precisely edit existing DNA sequences makes for more-accurate modifications, but it also makes it more difficult for regulators and farmers to identify a modified organism once it has been released. "With gene editing, there's no longer the ability to really track engineered products," says Jennifer Kuzma, who studies science policy at North Carolina State University in Raleigh. "It will be hard to detect whether something has been mutated conventionally or genetically engineered."

That rings alarm bells for opponents of genetically modified crops, and it poses difficult questions for countries trying to work out how to regulate gene-edited plants and animals. In the United States, the Food and Drug Administration has yet to approve any genetically modified animal for human consumption, and it has not yet announced how it will handle gene-edited animals.

Under existing rules, not all crops made by genome editing would require regulation by the US Department of Agriculture (see ). But in May, the agriculture department began to seek input on how it can improve regulation of genetically modified crops - a move that many have taken as a sign that the agency is re-evaluating its rules in light of technologies such as CRISPR. "The window has been cracked," says Kuzma. "What goes through the window remains to be seen. But the fact that it's even been cracked is pretty exciting."

Engineered ecosystems

Beyond the farm, researchers are considering how CRISPR could or should be deployed on organisms in the wild. Much of the attention has focused on a method called gene drive, which can quickly sweep an edited gene through a population. The work is at an early stage, but such a technique could be used to wipe out disease-carrying mosquitoes or ticks, eliminate invasive plants or eradicate herbicide resistance in pigweed, which plagues some US farmers.

Usually, a genetic change in one organism takes a long time to spread through a population. That is because a mutation carried on one of a pair of chromosomes is inherited by only half the offspring. But a gene drive allows a mutation made by CRISPR on one chromosome to copy itself to its partner in every generation, so that nearly all offspring will inherit the change. This means that it will speed through a population exponentially faster than normal (see 'Gene drive') - a mutation engineered into a mosquito could spread through a large population within a season. If that mutation reduced the number of offspring a mosquito produced, then the population could be wiped out, along with any malaria parasites it is carrying.

But many researchers are deeply worried that altering an entire population, or eliminating it altogether, could have drastic and unknown consequences for an ecosystem: it might mean that other pests emerge, for example, or it could affect predators higher up the food chain. And researchers are also mindful that a guide RNA could mutate over time such that it targets a different part of the genome. This mutation could then race through the population, with unpredictable effects.

"It has to have a fairly high pay-off, because it has a risk of irreversibility - and unintended or hard-to-calculate consequences for other species," says George Church, a bioengineer at Harvard Medical School in Boston. In April 2014, Church and a team of scientists and policy experts wrote a commentary in Science warning researchers about the risks and proposing ways to guard against accidental release of experimental gene drives.

At the time, gene drives seemed a distant prospect. But less than a year later, developmental biologist Ethan Bier of the University of California, San Diego, and his student Valentino Gantz reported that they had designed just such a system in fruit flies. Bier and Gantz had used three layers of boxes to contain their flies and adopted lab safety measures usually used for malaria-carrying mosquitoes. But they did not follow all the guidelines urged by the authors of the commentary, such as devising a method to reverse the engineered change. Bier says that they were conducting their first proof-of-principle experiments, and wanted to know whether the system worked at all before they made it more complex.

For Church and others, this was a clear warning that the democratization of genome editing through CRISPR could have unexpected and undesirable outcomes. "It is essential that national regulatory authorities and international organizations get on top of this - really get on top of it," says Kenneth Oye, a political scientist at the Massachusetts Institute of Technology and lead author of the Science commentary. "We need more action." The US National Research Council has formed a panel to discuss gene drives, and other high-level discussions are starting to take place. But Oye is concerned that the science is moving at lightning speed, and that regulatory changes may happen only after a high-profile gene-drive release.

The issue is not black and white. Micky Eubanks, an insect ecologist at Texas A&M University in College Station, says that the idea of gene drives shocked him at first. "My initial gut reaction was 'Oh my god, this is terrible. It's so scary'," he says. "But when you give it more thought and weigh it against the environmental changes that we have already made and continue to make, it would be a drop in the ocean."

Some researchers see lessons for CRISPR in the arc of other new technologies that prompted great excitement, concern and then disappointment when teething troubles hit. Medical geneticist James Wilson of the University of Pennsylvania in Philadelphia was at the centre of booming enthusiasm over gene therapy in the 1990s - only to witness its downfall when a clinical trial went wrong and killed a young man. The field went into a tailspin and has only recently begun to recover. The CRISPR field is still young, Wilson says, and it could be years before its potential is realized. "It's in the exploration stage. These ideas need to ferment."

Then again, Wilson has been bitten by the CRISPR bug. He says that he was sceptical of all the promises being made about it until his own lab began to play with the technique. "It's ultimately going to have a role in human therapeutics," he says. "It's just really spectacular."

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Three years ago, Bruce Conklin came across a method that made him change the course of his lab. Conklin, a geneticist at the Gladstone Institutes in San Francisco, California, had been trying to work out how variations in DNA affect various human diseases, but his tools were cumbersome.

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Though we've been living in the Space Age for more than half a century, going into space remains an extreme rarity. Fewer than 600 people have gone above the Kármán line - the point, about 62 miles above Earth, that marks the beginning of space - and all were put there by the U.S. or another nation's government.

But the rise of private spaceflight companies like Virgin Galactic and Space X means that the final frontier may soon be within reach of a great many more of us. The firms have announced plans to put private astronauts, a.k.a. space tourists, on orbital or suborbital flights within the next few years.

Initially, the cost of a ride on one of these rockets will be hundreds of thousands of dollars at a minimum. That puts the experience within reach of only the wealthiest people. But advances in rocket and capsule design are expected to lower the price to the point that people of more modest fortunes are able to afford a ticket.

Some projections put the global space tourism market at more than $34 billion by 2021.

What Space Tourists Can Expect

What exactly is in store for space tourists? The excitement of a rocket ride and a chance to experience weightlessness, for starters. And the bragging rights are hard to beat. But some say the biggest benefit of going into space is getting a dramatic new outlook on life on the fragile blue marble we call home. It's a perspective shift that could have profound implications not just for individuals but also for society at large.

"I personally believe the planetary perspective is going to be crucial to solving humanity's biggest challenges over the next century," says Virgin Galactic CEO George Whitesides. "I'm inspired that we'll take people up so they can experience that view, which is said to change your world view in a fundamental way."
Related: NASA Said No to My Astronaut Dream, So I Found Another Way
Billionaire computer engineer Charles Simonyi flew to the International Space Station aboard a Russian spacecraft with the assistance of a Vienna, Virginia-based firm called Space Adventures, and he echoes that sentiment. "It's great to go to space just because it's there," he says. "But I think space is our destiny and we will discover great benefits from it."

Flying High

Virgin Galactic plans to offer suborbital jaunts into space, with customers being treated to six minutes of weightlessness along with that one-of-a-kind view. The Las Cruces, New Mexico-based company says more than 600 customers have signed up, including Leonardo DiCaprio, Katy Perry, Ashton Kutcher, and superstar physicist Stephen Hawking. The price of a ticket stands at $250,000, with registration open for anyone who has that kind of extra cash on hand.

On June 1, Virgin successfully tested SpaceShipTwo Unity. The six-passenger spacecraft glided more than nine minutes to the ground after being released from an airplane flying at 50,000 feet. The company plans to make several more unpowered tests before allowing Unity's rocket engine to fire up so that, following its release from the plane, it can soar into space.

The company has been promising flights since unveiling SpaceShipTwo in 2009. But a series of bruising setbacks, including a 2014 crash that claimed a test pilot's life, extended the craft's test phase.

Virgin CEO Richard Branson said on July 5 that he hopes to see sp ace tourists flying on Virgin by the end of 2018. But other executives at the firm seem reluctant to commit to that. As Whitesides put it to NBC News MACH, "Once when we're at a place where we're comfortable with powered flights, we'll be ready to begin commercial operations."

Downs and Ups

Midland, Texas-based XCOR Aerospace sought to offer suborbital flights similar to those envisioned by Virgin Galactic. But in 2016, the company halted development of its space-plane, Lynx. On July 5, it announced that all remaining employees had been laid off but stopp ed short of saying it was out of business.
Related: Take a Tour of NASA's Full-Size Mockup of the International Space Station
Between 2001 and 2009, Space Adventures arranged for seven paying customers (including Charles Simonyi) to blast into space for a stint aboard the ISS. Each of these private astronauts got to the station aboard a Russian Soyuz capsule. Space Adventures has unspecified plans to send up more customers but can't now. Since the end of NASA's Space Shuttle program in 2011, all seats on Soyuz have been filled by American and Russian astronauts.

Amazon CEO Jeff Bezos has been eyeing the space tourist market with his private space company, Blue Origin. The company recently posted computer renderings of the opulent interior of its reusable New Shepard capsule configured with six plush leather chairs and six enormous windows.

Blue Origin has yet to say exactly when flights might begin or how much they would cost. Bezos said in March that he'd like to have his first customer flights next year. The company has a sign-up form for those interested in reserving a seat.

Of all companies offering, or expecting to offer, flights into space, SpaceX may have the most compelling story. Earlier this year, CEO Elon Musk announced that the company had accepted payment from two customers for a weeklong flight around the moon and back to Earth, largely retracing the path taken by Apollo 8 astronauts in 1968.

Musk has said that the mission could come as soon as 2018. Some are dubious, however, given SpaceX's reputation for offering overly optimistic schedules. How much the customers paid for the flight is unknown, but estimates have ranged from $80 million to $175 million per seat.

SpaceX has also announced the even more ambitious goal of sending colonists to Mars starting in 2025. Musk has said that once the company is able to build its massive 100-person Mars Colonial Transporter spacecraft, a trip to the Red Planet will cost about $500,000 - roughly the price of a middle-class house in California - with the goal of eventually bringing the price down to $100,000.

Almost Space

Tucson, Arizona-based World View Enterprises has announced plans to send passengers to an altitude of 100,000 feet in a luxury gondola suspended from a gigantic helium balloon. It's not quite space, but at that altitude, it's possible to see the blackness of space and the curvature of the earth. Eight customers would spend two hours ascending, two hours in cruise, and another hour or two returning to the ground.

Though lacking the cachet of true spaceflight, the World View flights promise a more refined experience; customers would be able to clink champagne glasses while taking in the view from enormous picture-frame windows and posting their photos to social media using onboard Wi-Fi.
Related: This Aspiring Astronaut Has Taken Some Dramatic Steps to Make His Dream Come True
World View says it hopes to begin manned testing in 2018 but offers no specific dates for the tourist flights. A ticket is projected to cost $75,000. The company's co-founder and chief technology officer, Taber MacCallum, says the target customer is "the Baby Boomer who's already bought their Ferrari and bought their third house and are looking for an experience to talk about and share."

Finally, there's Zero Gravity Corporation, an Arlington, Virginia-based company that already offers flights aboard a specially modified Boeing 727 that dives steeply to give paying passengers brief periods of weightlessness. As with the World View balloons flights, these parabolic flights aren't actually trips into space. But with a ticket for the experience running a relatively modest $5,000, it might be the cheapest way to get a sense of what it's like above the Kármán line.

Zero G flights take off weekly from airports across the U.S., including Orlando Sanford International near Orlando, Florida, McCarran International near Las Vegas, and Moffett Federal Airfield near San Francisco.
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So you want to be a space tourist? Here are your options

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Though we've been living in the Space Age for more than half a century, going into space remains an extreme rarity. Fewer than 600 people have gone above the Kármán line - the point, about 62 miles above Earth, that marks the beginning of space - and all were put there by the U.S.

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Advancements in the Research of 4D Printing- A Review

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Advancements in the Research of 4D Printing- A Review

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http://iopscience.iop.org/article/10.1088/1757-899X/376/1/012123/pdf

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Pet Cloning is Bringing Human Cloning a Little Bit Closer  

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Pet Cloning is Bringing Human Cloning a Little Bit Closer  

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Antonio Regalado
March 13,2018

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People are copying pets to preserve a physical, and spiritual, connection to dead children.

When Barbra Streisand revealed to Variety magazine that she'd had her dog cloned for $50,000, many people learned for the first time that copying pets and other animals is a real business.

That's right: you can pay to clone a dog, a horse, or a top beef bull and get a living copy back in a matter of months.

The story that sent shivers up my spine, though, came out a few days later. It was about Monni Must, a Michigan portrait photographer who paid to clone Billy Bean, a Labrador retriever that had belonged to her oldest daughter, Miya.

Miya had committed suicide 10 years earlier. To Must, cloning the elderly dog was a way to keep her daughter's memory alive and, she says, to "protect" her grief.

During the cloning procedure, Must received updates, including sonograms of the developing puppy. The time line seemed full of profound coincidences. Veterinarians detected the clone's heartbeat on Miya's birthday, October 11. The puppy was born in November, the same month Miya killed herself.

"It's a sign. For me, it's a sign that Miya is involved and aware," Must told me.

Alarm bells went off in my head. Must wasn't just cloning a pet. She was trying to preserve a lost child. It seemed awfully close to a real human cloning scenario, one in which a heartbroken parent tries to replace a son or daughter who dies early.

I shot a question to Jose Cibelli, an animal cloning scientist at Michigan State University: Is it time to worry about human cloning again?

Cibelli quickly e-mailed back: "Yes."

Shudder to think

I met Cibelli 15 years ago, when I was among a pack of journalists covering cloning nonstop. Back then, it seemed possible that someone might try to copy a human being at any moment. There was a loud-mouthed Italian fertility doctor named Antinori who said he was trying, and a UFO cult called the Raëlians had a human cloning company, Clonaid; it seemed all too plausible when they pranked the media with claims to have created a clone baby named Eve. In 2002, the National Academies issued an emergency report on the situation.

But human cloning never happened. The reason is clear in retrospect. In the basic cloning procedure, like that used to create Dolly the sheep in 1996, scientists take an entire adult cell and inject it into an egg that's been relieved of its own DNA. The resulting embryo is a clone.

But that process is inefficient. In many animals, only one in 100 cloned embryos ever leads to a live birth. Some embryos expire in the IVF dish. Others wither in the womb. Of those that are born, a few suffer from abnormalities and quickly die.

You would "shudder to think," a 2001 article in the New York Times said, "what might happen if humans are cloned with today's techniques."

Nevertheless, cloning moved forward in cattle and pet dogs. That is because eggs can be collected in large enough numbers to let companies overcome the technology's inherent inefficiency. Failed clones are just a cost of doing business.

The cause of the problems is better understood today. For a skin cell to be a skin cell, it doesn't need the full complement of genes. So many are simply shut off. The reason cloning works at all is that an egg has a remarkable ability to turn genes back on through a process called reprogramming. Yet the egg has only hours to do the job, and some genes are resistant.

It is these resistant genes, still blocked and unavailable to play their role in the developing embryo, that "are believed to be responsible for the demise of clones," Cibelli says.

Something changed

That's also where the recent breakthroughs come in. Cibelli pointed me to the work of Yi Zhang, a stem-cell biologist at Boston Children's Hospital and an investigator at the Howard Hughes Medical Institute. He said Zhang has found chemicals that, if added to an egg, can help release the blocked genes.

In Zhang's hands, addition of these "modifiers" has led to dramatic improvements in cloning-wiping out barriers present in the adult cells. Zhang first tried it with mice. Instead of about 1 percent of cloned embryos leading to a mouse pup, he says, now 10 percent of them do.

"The gain in efficiency is tremendous," says Zhang, who says he filed a patent based on the discovery.

Zhang then tried the process on human eggs. In 2015, his team recruited four women to have eggs drawn from their ovaries. Into these, they injected skin cells from other people.

Without the gene-releasing molecules, the cloned embryos never developed correctly. With the modifiers, though, about a quarter of them did. "We tried to wipe out the barriers in the adult cells," he says. "Bottom line: we would have failed otherwise."

To be very clear, Zhang isn't planning to make babies. Instead, his objective in cloning speck-size human embryos is to obtain their stem cells. Known as "therapeutic cloning," it's a way to create powerful embryonic stem cells genetically identical to those of the donor adult-say, as a source of replacement tissue.

Therapeutic cloning is not a new idea. Cibelli himself was the first to try it (and fail) 15 years ago. When it didn't work, scientists moved toward other ways of making stem cells by reprogramming skin cells in the lab. Suddenly, though, cloning for stem cells is no longer the wackadoodle scheme it once was. With higher efficiency, doctors might actually use it to make matching tissue for people who can afford it, says Zhang. He's starting a company, NewStem, to begin banking cloned stem cells.

"Before, it was theoretically possible, but you'd have to use a lot of eggs, so it wasn't a reality," says Zhang. "Now, with the efficiency, it becomes a reality."

Monkey clones

We can make cloned human embryos pretty well. Could we go further and grow those embryos into a baby? A clue came in January of 2018, when researchers in China cloned our animal cousins-monkeys-for the first time. Pictures of two cute baby primates, Zhong Zhong and Hua Hua, quickly spread around the world.

Qiang Sun and Mu-ming Poo | Chinese Academy of Sciences | Cell Press

Why had the Chinese succeeded where every previous attempt to clone monkeys had failed? The answer was they'd used Zhang's efficiency-enhancing molecules.

Not all the problems have been solved. The Chinese managed to create the animals by starting with skin cells of an aborted monkey fetus. But two other clones, made from an adult animal's cells, died shortly after birth. There's little detail available on why those two monkeys died. But it's a safe bet it was somehow to do with incomplete reprogramming of the adult cells.

In Zhang's view, it would still be crazy and impractical (and illegal) to try to clone a person. Despite the higher efficiency, he notes that Chinese teams used 63 surrogate mothers and 417 eggs to make two monkey clones. Just imagine arranging for dozens of human surrogates and egg donors.

"No society could accept this," says Zhang. "On the other hand, if you are asking me, Can you improve the efficiency even more? Well, the answer is yes. My answer is that eventually, from a technology point of view, human cloning will be possible."

Cloning motivations

Creating a human clone isn't only a question of technology. You'd also need a reason to do it, experts willing to help, and someone to fund it all.

Wildcatting billionaires might be the easiest part to arrange. In March, the CBS program 60 Minutes aired a segment about La Dolfina, an Argentinian polo team whose players all ride copies of the same horse. The entrepreneur behind the horse cloning, Texas businessman D. Alan Meeker, told CBS that he's "been asked by some of the wealthiest people on the planet to clone a human being." Meeker said he'd refused. His reason: no one would tell him why they wanted a clone.

But we know one reason-maybe the most powerful of all. When I spoke by phone to Must, the photographer, she recounted her devastation at her daughter's suicide.

Must had inherited Miya's dog, Billy Bean, and told me the idea of cloning came to her suddenly, years later, when the dog was about to turn 14. "I feared everyone was going to forget Miya, that am I going to forget Miya," Must said. "I thought I was going to lose the dog, and I was literally falling part. It was a lightning bolt: oh my God, I am going to clone her. I was just desperate."

Labrador retriever Billy Bean and her clone, Gunni.

Must eventually had a veterinarian collect a sample of the dog's skin tissue and sent it to a company called PerPETuate. For a $1,300 fee, PerPETuate prepares a cell line from a pet's skin and stores the cells in liquid nitrogen for later cloning. The service is, in effect, an inexpensive way to hold onto an animal's DNA while you decide if you'll pay the full $50,000 cloning cost. PerPETuate founder Ron Gillespie says he's storing frozen tissue from dogs, cats, and even a lion from a Mexican zoo. Must isn't the only person to clone a dog belonging to a dead child, he says. The company will not accept human cells, however. Not from bereaved parents or anyone else.

"We've gotten many requests," says Gillespie. "I say we don't do it. And when people press me where they can do it, I say 'I don't know.' I just totally dismiss it. One of the biggest complaints we have about this is that it is going to lead to human cloning, and people are very opposed to that, beginning with me."

Billy Bean's cells ended up getting shipped to ViaGen Pets, a Texas company that provides the cloning service. In September 2017, Must learned that cloned Billy Bean embryos had been transferred to a canine surrogate. Two months later, she picked up the new puppy. The dog "has a real soul and is everything my daughter was-fun, social, kind, and people gravitate to her," she says. "I feel that I still have that touchable, tactile connection and not just a spiritual connection."

I finally asked Must: Would she have cloned Miya if she'd had the chance?

She said it's not a question she has an answer to. "When you have a child who dies, you are not in a good place. You are not in a place to make a rational decision," she says.

In fact, she admits people thought she'd gone "over the edge" when she resolved to clone the dog. "It was a particularly desperate attempt on my part. My other daughters thought I had lost my marbles," she says. "But it worked. It is kind of scary to think of what this means."

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Pet cloning is bringing human cloning a little bit closer

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When Barbra Streisand revealed to Variety magazine that she'd had her dog cloned for $50,000, many people learned for the first time that copying pets and other animals is a real business. That's right: you can pay to clone a dog, a horse, or a top beef bull and get a living copy back in...

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11/05/14

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Special 'ink' developed at CityU Enables World's First 4D Printing For Ceramics

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Special 'ink' developed at CityU Enables World's First 4D Printing For Ceramics

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https://www.cityu.edu.hk/cityupdate/media/news/2018/08/30/special-ink-developed-cityu-enables-worlds-first-4d-printing-ceramics

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Noel Merino

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Direct 4D printing via active composite materials

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Direct 4D printing via active composite materials

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Direct 4D printing via active composite materials

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We describe an approach to print composite polymers in high-resolution three-dimensional (3D) architectures that can be rapidly transformed to a new permanent configuration directly by heating.

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Kimberly Leonard
August 4, 2016

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How much are SpaceX tourists actually paying to fly around the moon?

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How much are SpaceX tourists actually paying to fly around the moon?

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Rachel Becker

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Two mystery space tourists put down a " significant deposit" with SpaceX to take a round-trip around the Moon, CEO Elon Musk announced yesterday. Musk didn't say much about the two unidentified passengers, let alone how much money they're shelling out for their Moon voyage. Turns out, it's remarkably difficult to guess the costs of human spaceflight.

"There's not just a line item that says, 'Send this person to space.'"

That's because, unsurprisingly, there's a lot that goes into launching someone into space. There are the obvious costs: the spacecraft, the rocket, and the fuel. But then there are the less obvious, just as key, costs: the years and equipment needed to train the astronauts, building and maintaining the launchpad, paying the people on the ground in mission control, having rescue plans and personnel ready to get the astronauts or space tourists to safety if there's an emergency. And that's just the short list.

"It's always a more complex answer," Daniel Huot, a spokesperson for NASA, tells The Verge. "There's not just a line item that says, 'Send this person to space.'"

Here's what we do know: while Musk wouldn't specify an exact price, he did say that the around-the-Moon mission could cost roughly the same or a bit more than a crewed trip to the International Space Station. SpaceX declined an emailed request for clarification.

So what does that mean? Right now NASA pays the Russian space agency Roscosmos about $81 million and change for a round-trip ticket in a Soyuz capsule. The latest five seats NASA bought in bulk were a little cheaper, about $74.7 million per seat. Another spokesperson for NASA, Kathryn Hambleton, told The Verge in an email that the ticket price includes:

Training to operate the spacecraft

Use of the launchpad and launch support services

Flight control, docking, and undocking services

Air, consumables, and life support en route

Standby emergency services for a rescue in orbit, or during landing

Medical services after landing

The variable weight of the crew and their cargo to and from the station

The reason why NASA relies on Roscosmos is that the US space agency hasn't had a vehicle of its own to ferry astronauts to and from the ISS since 2011, when the Space Shuttle program was shuttered. NASA is hoping the $81 million price tag will drop in the future by partnering with private companies like SpaceX and Boeing through the Commercial Crew Program.

NASA estimates that a round-trip ticket to the ISS on the SpaceX Crew Dragon or the Boeing CST-100 Starliner would cost about $58 million. A spokesperson for Boeing could not confirm the ticket price, and SpaceX declined to comment.

How much would this longer trip cost?

A one-way trip to the ISS, however, covers a distance of roughly 220 miles. Musk said yesterday that the SpaceX lunar trip would brush past the surface of the Moon and venture deeper into space, before looping back to Earth - a distance of approximately 300,000 to 400,000 miles. (It's not clear how they arrived at those numbers, considering that a one-way trip to the Moon when it's closest to Earth is about 225,623 miles, according to NASA.)

How much would this much longer trip cost? Space Adventures, a travel agency that arranges space journeys with Roscosmos for private citizens, tells The Verge the price tag is more than double the cost of a trip to the ISS: about $175 million dollars per seat. The company, which has already sent seven individuals to the space station, plans to send tourists around the Moon by 2020 - and that's how much they're going to charge.

"We cannot be more specific as there are many variables, including destination, vehicle, duration and other options," Stacey Tearne, a spokesperson for Space Adventures, wrote in an email to The Verge.

One of the variables, which could shoot up the price of any space mission, is of course, delays. And as we know, Musk has a bit of a problem with deadlines.
Update 1:10PM EST, 2/28: Updated to reflect the fact that a SpaceX spokesperson replied to emailed inquiries after the story was published, but declined to comment.

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How much are SpaceX tourists actually paying to fly around the Moon?

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Two mystery space tourists put down a " significant deposit" with SpaceX to take a round-trip around the Moon, CEO Elon Musk announced yesterday. Musk didn't say much about the two unidentified passengers, let alone how much money they're shelling out for their Moon voyage.

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What Is Geoengineering? 1 Minute! Full Explanation!

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Controversial CRISPR "Gene Drives" Tested in Mammals for the first time

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Controversial CRISPR "Gene Drives" Tested in Mammals for the first time

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By: Ewen Callaway
7/10/18

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A controversial technology capable of altering the genomes of entire species has been applied to mammals for the first time. In an article posted on the bioRxiv preprint server on 4 July, researchers describe developing 'gene drives'-which could be used to eradicate problematic animal populations-in lab mice using the CRISPR gene-editing technique.

Gene drives ensure that chosen mutations are passed on to nearly all an animal's offspring. They have already been created in mosquitoes in the lab, as a potential malaria-control strategy. Researchers have raised the possibility that the technology could help to kill off invasive rats, mice and other rodent pests. But the latest study dashes hopes of that happening any time soon, say scientists. The technique worked inconsistently in lab mice, and myriad technological hurdles remain before researchers could even consider releasing the tool in the wild.

"There's an indication it could work, but it's also sobering," says Paul Thomas, a developmental geneticist at the University of Adelaide in Australia, who was not involved in the research. "There is a lot more to do before you could consider gene drives for a useful tool for population control of rodents." His lab is doing similar work, as part of an international consortium to use gene drives to combat invasive rodents.

Gene drives work by ensuring that a higher proportion of an organism's offspring inherit a certain, 'selfish' gene than would happen by chance, allowing a mutation or foreign gene to spread quickly through a population. They occur naturally in some animals, including mice, where they can cause death or infertility. But the revolutionary CRISPR-Cas9 gene-editing tool has led to the development of synthetic gene drives that are designed to eliminate problem species, such as malaria-transmitting mosquitoes, from the wild by, for instance, ensuring that offspring are infertile. The technology has attracted controversy- and even a failed attempt to ban its use globally -because, if released in the wild, organisms carrying gene drives might be hard to contain.

A team led by Kim Cooper, a developmental geneticist at the University of California, San Diego, did not attempt to develop a gene drive to make lab mice ( Mus musculus) infertile. Rather, the researchers' goal was to create a test bed for the technology, which they say could also be useful in basic research: they biased the inheritance of a mutation that gives mice all-white coats, instead of infertility.

CRISPR-based gene drives use the gene-editing tool to copy a mutation on one chromosome to the second of the pair, usually during an animal's early development. When Cooper's team attempted this in mouse embryos, the mutation was not always copied correctly, and the process worked only in female embryos.

The team estimated that this could lead to a mutation being transmitted to about 73% of a female mouse's offspring, on average, instead of the usual 50% for most genes operating under the normal rules of inheritance. Cooper declined to comment on her team's work, because it has not yet been published in a peer-reviewed journal.

Tony Nolan, a molecular biologist at Imperial College London who is part of a team developing gene drives in malaria-carrying mosquitoes, is excited to see that gene drives can, at least, work in rodents. Even if the technology doesn't become an eradication tool, it could be more efficient than existing technologies at producing transgenic lab animals that model diseases caused by multiple mutations, he says.

Other researchers agree that the study is important, but say it also shows just how far the technology has to go in rodents. "Could you imagine this gene drive in the wild? That's not going to happen," says Gaétan Burgio, a geneticist who works on CRISPR at the Australian National University in Canberra. The relatively low efficiency of the technique means it would take many generations for the gene drive to spread through an entire rodent population, leaving ample time for species to evolve resistance.

Thomas describes the results as a "reality check" for efforts to develop gene drives in rodents. "It gives an indication to how much further there is to go," he says. Future work should seek to improve efficiency, as well as understand why the technique doesn't work in male mice, Thomas adds.

He is a member of a consortium called Genetic Biocontrol of Invasive Rodents, or GBIRd, that hopes to deploy gene drives against rats and mice.

CRISPR gene drives aren't the consortium's only strategy for dealing with invasive rodents. GBIRd member David Threadgill, a geneticist at Texas A&M University in College Station, and his team are working with a gene drive that occurs naturally in mice, called the t-haplotype. The researchers plan to modify this selfish gene to create daughterless mice: females carrying two copies will give birth only to males, potentially leading to a population crash.

Should gene-drive technology prove effective at controlling rodents, islands are an ideal test bed, says Heath Packard, director of Island Conservation in Santa Cruz, California, a GBIRd partner that focuses on eradicating invasive pests. Rodent pesticides that have eliminated problem mice and rats on small islands are too risky to use on larger islands, with complex ecosystems and large human populations, Packard says. Gene drives, which could be contained on islands, are still a technology worth investigating. "We're hopeful that this might be a tool that could serve the island restoration community," he says, "but we don't know if it's going to work."
This article is reproduced with permission and was first published on July 6, 2018.

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Controversial CRISPR "Gene Drives" Tested in Mammals for the First Time

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A controversial technology capable of altering the genomes of entire species has been applied to mammals for the first time. In an article posted on the bioRxiv preprint server on 4 July, researchers describe developing 'gene drives'-which could be used to eradicate problematic animal populations-in lab mice using the CRISPR gene-editing technique.

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Harvard Scientists Moving Ahead on Plans for Atmospheric Geoengineering Experiments

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Harvard Scientists Moving Ahead on Plans for Atmospheric Geoengineering Experiments

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MIT Technology Review

March 24, 2017

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Harvard University professor David Keith

A pair of Harvard climate scientists are preparing small-scale atmospheric experiments that could offer insights into the feasibility and risks of deliberately altering the climate to ease global warming.

They would be among the earliest official geoengineering-related experiments conducted outside of a controlled laboratory or computer model, underscoring the growing sense of urgency among scientists to begin seriously studying the possibility as the threat of climate change mounts.

Sometime next year, Harvard professors David Keith and Frank Keutsch hope to launch a high-altitude balloon, tethered to a gondola equipped with propellers and sensors, from a site in Tucson, Arizona. After initial engineering tests, the "StratoCruiser" would spray a fine mist of materials such as sulfur dioxide, alumina, or calcium carbonate into the stratosphere. The sensors would then measure the reflectivity of the particles, the degree to which they disperse or coalesce, and the way they interact with other compounds in the atmosphere.

The researchers first proposed these balloon experiments in a 2014 paper. But at a geoengineering conference in Washington, D.C., on Friday, Keith said they have begun engineering design work with Arizona test balloon company World View Enterprises. They've also started discussions about the appropriate governance structure for such an experiment, and they plan to set up an independent body to review their proposals.

"We would like to have the first flights next year," he said at the Forum on U.S. Solar Geoengineering Research, held at the Carnegie Endowment for International Peace.

In an earlier interview with MIT Technology Review, Keith stressed that the experiments would not be a binary test of geoengineering itself. But they should provide useful information about the proposed method that he has closely studied, known as solar radiation management.

The basic idea is that spraying certain types of particles into the stratosphere could help reflect more heat back into space. Scientists believe it could work because nature already does it. Large volcanic eruptions in the past have blasted tens of millions of tons of sulfur dioxide into the sky, which contributed to lower global temperatures in subsequent months.

What's less clear is how precisely the technique could control worldwide temperatures, what materials would work best, and what the environmental side effects might be. Notably, previous volcanic eruptions have also decreased precipitation levels in parts of the world, and sulfur dioxide is known to deplete the protective ozone layer.

Keith has previously used computer modeling to explore the possibility of using other materials that may have a neutral impact on ozone, including diamond dust and alumina. Late last year, he, Keutsch, and others published a paper that found using calcite, a mineral made up of calcium carbonate, "may cool the planet while simultaneously repairing the ozone layer."

The balloon tests could provide additional insight into how these chemicals actually interact with precursors to ozone in the real world and offer additional information that could help refine their understanding of solar geoengineering, he says: "You have to go measure things in the real world because nature surprises you."

Keith stresses that it's too early to say whether any geoengineering technologies should ever be deployed. But he has argued for years that research should move ahead to better understand their capabilities and dangers, because it's possible they could significantly reduce the risks of climate change. He stressed that the experiments would have negligible environment impacts, as they will involve no more than a kilogram of materials.

Funding for the initial experiments would come from grants that Harvard provided Keith and Keutsch as new professors. Additional funds may come from Harvard's Solar Geoengineering Research Program, a multidisciplinary effort launching this spring to study feasibility, risks, ethics, and governance issues surrounding geoengineering. As of press time, it had raised more than $7 million from Microsoft cofounder Bill Gates, the Hewlett Foundation, the Alfred P. Sloan Foundation, Harvard-internal funds, and other philanthropists.

Geoengineering critics argue that the climate system is too complex to meddle with, that the environmental risks are too high, or that even talking about technological "fixes" could ease pressure to cut greenhouse gas emissions.

Only two known experiments have been carried out in the open air to date that could be considered geoengineering-related: University of California, San Diego, researchers sprayed smoke and salt particles off the coast of California as part of the E-PEACE experiment in 2011, and scientists in Russia dispersed aerosols from a helicopter and car in 2009. The so called SPICE experiment in the United Kingdom was quickly scuttled in 2012, following public criticism and conflict of interest accusations after several of the scientists applied for a related patent.

In an earlier interview, Jane Long, a former associate director at Lawrence Livermore National Laboratory, stressed that researchers moving forward with geoengineering experiments need to go to great lengths to ensure proper public notification, opportunities for input, and appropriate oversight, particularly if they're relying on private funds. But she said it's time to begin seriously studying the technology's potential given the growing dangers of climate change.

"We should have started a decade ago," she said. "It's critical to know as much as we can as soon as we can."

Credit

Image courtesy of Arizona State University

James Temple Senior Editor, Energy

I am the senior editor for energy at ... and columnist at the MIT Technology Review. I'm focused on renewable energy and the use of technology to combat climate change. Previously, I was a senior director at the Verge, deputy managing editor at Recode, More San Francisco Chronicle. When I'm not writing about energy and climate change, I'm often hiking with my dog or shooting video of California landscapes.

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Harvard scientists are gearing up for some of the first outdoor geoengineering experiments

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A pair of Harvard climate scientists are preparing small-scale atmospheric experiments that could offer insights into the feasibility and risks of deliberately altering the climate to ease global warming. They would be among the earliest official geoengineering-related experiments conducted outside of a controlled laboratory or computer model, underscoring the growing sense of urgency among scientists to begin seriously studying the possibility as the threat of climate change mounts.

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Richard Hollingham

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Right now, one of the most exciting space facilities in the world is a World War Two hangar in the Mojave Desert in California.

The wooden hangar belongs to Xcor, one of the start-up companies building rocket planes to fly tourists into space. In the hangar next door, you can glimpse Virgin Galactic's spaceplane, slung beneath its carrier aircraft. Further along the runway, Microsoft billionaire Paul Allen's company, Stratolaunch, is developing a new space launch system. Eleven other small space businesses are spread around the site at the Mojave Air and Space Port.

Later this year, Virgin aims to fly its first paying passengers into space. The experience will not come cheap. Virgin Galactic is charging $250,000 for the privilege of experiencing five minutes of weightlessness; Xcor plans to charge $95,000 for a ride in its two-seater rocket ship. The cost alone puts this fledgling space-tourism industry beyond the means of most of us.

So it is easy to dismiss the whole enterprise as private jets in space rather than benefits for all mankind (as BBC Future readers have done on our Facebook page). But having followed the development of the private space industry for the last 20 years, and after a recent visit to the Mojave Air and Space Port for a BBC radio programme, I thought it was worth outlining why I think space tourism matters.

1. It frees space ambitions from traditional burdens
The audacious plan to put men on the Moon was championed by politicians and backed with billions of taxpayer dollars. By the time men had actually stepped onto the lunar surface, Nasa's budget was already being cut. Subsequent US, Russian and European space programmes - from the Shuttle to the International Space Station (ISS) - have suffered from political compromise and lack of ambition.

Private space travel companies using reusable spaceplanes could help boost space exploration (AFP/Getty Images)

Private spaceflight, on the other hand, is unburdened by the favour of taxpayers or whims of politicians. If the company can raise the cash, it can build a spacecraft. Inevitably, this free market favours people who already have a lot of money. But that is not true of all the companies in the private space business.

"We don't have a multi-billionaire funding us," admits the CEO of Xcor, Jeff Greason. For him, building a sub-orbital tourist craft is part of a long-term strategy. "We started examining how a fully-reusable orbital system would look and realised we would need to develop earlier versions of that to learn how to build them," he says. "Those earlier versions also have to make money."

2. Failure is now an option
Nasa is forever burdened with the phrase "failure is not an option". Private companies have no such restrictions until the money runs out.

The entrance to the Mojave Air and Space Port is dominated by a reminder that not all space projects succeed. Resembling a giant white traffic cone, the Rotary Rocket is one of the most peculiar flying machines ever built - probably best described as half-helicopter, half-spacecraft, and if you were being cruel, you might also call the concept half-baked.

It was one of the first spacecraft to be developed at Mojave and, in 1999, made some brief atmospheric test flights. The engineering proved sound but funding problems caused the company to fold. Today it is gathering desert dust in a small memorial garden.

One person who worked on the Rotary is Kevin Mickey, President of Scaled Composites - the company now building Virgin's spaceplane. "I look at this, and I'm proud of it," says Mickey, as we stand beside the white conical spacecraft.

"One of the hurdles in today's society is an intolerance for risk and failure and if you are truly going to innovate, you are going to fail sometimes," he says. The carbon composite materials technology that went into the Rotary is now being adapted for Scaled Composite's aircraft and spaceplanes, so the expertise has not totally gone to waste.

3. It will inspire a new generation of engineers
The spaceport looks more like a college campus than a space centre. Take, for example, 26-year-old Xcor engineer, Jeremy Voigt. He proudly shows me one of the rocket engines he is helping to develop: currently, it's a mass of pipes, wires and valves.

Rockets can only be launched once - and can cost up to $12m a time (AFP/Getty Images)

"It's the engineer's dream job," he says. "Most engineers sit behind a desk all day, I don't. I get to come out here in the shop, turn wrenches and fire rocket engines."

He looks around the crowded hangar, crammed with bits of rocket motor and partially constructed spaceplane. "If I was at Nasa, I would be part of a large team of engineers working on something," he says excitedly. "Here I actually lead the rocket test, I get to push the button."

The way of working at Mojave, in small teams with limited resources, is completely different to the way the space agencies work. Many people compare what is going on at Mojave with the early days of Silicon Valley and it is easy to draw parallels between the garage where Steve Jobs and Steve Wozniak built the first Apple computer, and the Xcor workshop. Maybe the young engineers here will have equally world-changing effects.

4. The cost of reaching space will go down
Right now, if you want to launch a satellite, it will cost upwards of $12m and that is before the compulsory insurance (which can sometimes double the price). Not only can conventional space rockets only be used once, they are extremely expensive to launch - and there is limited competition.

Compare that with the $250,000 cost of a flight on the reusable Virgin spaceplane. Scientific institutions have already signed up to fly experiments on these sub-orbital flights. If the next generation of space planes can reach orbit then that will massively reduce the cost of getting into space.

This means we will be able to launch satellites, spacecraft and space exploration missions for a fraction of the cost. The final frontier could finally become economically viable to a lot more people.

It is certainly something that gets CEO of Virgin Galactic and ex-Nasa employee, George Whitesides excited. "By lowering the cost of space access, we'll be able to do things like sending little nanosats all over the Solar System and do all this incredible science, that is so expensive now," he says. "If we are able to tackle some of these challenges by demonstrating access to space technologies, then I think that will be profound."

5. Hypersonic travel could become a possibility
Remember the idea that you can take off from London, fly into space and touch down in San Francisco an hour or so later? When discussing technologies that are promised but never quite deliver, a close runner-up behind flying cars has to be so-called sub-orbital point-to-point travel. Could the space tourism companies at Mojave finally help make this dream a reality? George Whitesides thinks so: "This is fundamentally transformational for humanity," he tells me.

How much would you be willing to pay for a view like this? (Nasa)

"I really think of our customers as pioneers, opening up the new frontier," he says. "For one thing, everyone would like to get there faster, another reason is that you're not chugging through the atmosphere for 12 hours, so there could be environmental benefits to that."

But few people are going to pay $250,000, or even $95,000, for a flight to San Francisco, however fast. Space tourism companies counter with the argument that as the technology evolves, costs will inevitably come down. The history of aviation suggests this is indeed the case.

"Most technologies at the front end are funded by wealthier folks," says Whitesides. "If you go back to the dawn of commercial aviation, the real adjusted cost of crossing the Atlantic was $10,000 or if you look at the early cellphones they were thousands of dollars, now you can get them for free if you sign up for a contract."

Right now, the space companies are only on their first-generation rocket planes. By the 10th generation, point-to-point travel via space may become a reality.

6. It will provide a new view of our planet
It is widely accepted that one of the greatest achievements of the Apollo Moon programme was the view of the Earth from space. Apollo 8 astronaut Bill Anders summed up the impact of the pictures captured by his mission: "We came all this way to explore the Moon," he said, "and the most important thing is that we discovered the Earth". The images put us in our place, a blue marble against the backdrop of nothingness.

Every astronaut I have interviewed talks about how seeing the Earth from space changed their view of the world. So imagine what would happen if we started sending business and political leaders into space and back? Would that view of the world change them in the way it affected astronauts? And as a result, could it influence the decisions they make on border disputes, pollution or climate change?
If you would like to comment on this, or anything else you have seen on Future, head over to our Facebook or Google+ page, or message us on Twitter.

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Right now, one of the most exciting space facilities in the world is a World War Two hangar in the Mojave Desert in California. The wooden hangar belongs to Xcor, one of the start-up companies building rocket planes to fly tourists into space.

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MIT students fortify concrete by adding recycled plastic

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MIT students fortify concrete by adding recycled plastic

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Jennifer Chu
October 25, 2017

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Discarded plastic bottles could one day be used to build stronger, more flexible concrete structures, from sidewalks and street barriers, to buildings and bridges, according to a new study.

MIT undergraduate students have found that, by exposing plastic flakes to small, harmless doses of gamma radiation, then pulverizing the flakes into a fine powder, they can mix the irradiated plastic with cement paste and fly ash to produce concrete that is up to 15 percent stronger than conventional concrete.

Concrete is, after water, the second most widely used material on the planet. The manufacturing of concrete generates about 4.5 percent of the world's human-induced carbon dioxide emissions. Replacing even a small portion of concrete with irradiated plastic could thus help reduce the cement industry's global carbon footprint.

Reusing plastics as concrete additives could also redirect old water and soda bottles, the bulk of which would otherwise end up in a landfill.

"There is a huge amount of plastic that is landfilled every year," says Michael Short, an assistant professor in MIT's Department of Nuclear Science and Engineering. "Our technology takes plastic out of the landfill, locks it up in concrete, and also uses less cement to make the concrete, which makes fewer carbon dioxide emissions. This has the potential to pull plastic landfill waste out of the landfill and into buildings, where it could actually help to make them stronger."

The team includes Carolyn Schaefer '17 and MIT senior Michael Ortega, who initiated the research as a class project; Kunal Kupwade-Patil, a research scientist in the Department of Civil and Environmental Engineering; Anne White, an associate professor in the Department of Nuclear Science and Engineering; Oral Büyüköztürk, a professor in the Department of Civil and Environmental Engineering; Carmen Soriano of Argonne National Laboratory; and Short. The new paper appears in the journal Waste Management.

"This is a part of our dedicated effort in our laboratory for involving undergraduates in outstanding research experiences dealing with innovations in search of new, better concrete materials with a diverse class of additives of different chemistries," says Büyüköztürk, who is the director of Laboratory for Infrastructure Science and Sustainability. "The findings from this undergraduate student project open a new arena in the search for solutions to sustainable infrastructure."
An idea, crystallized
Schaefer and Ortega began to explore the possibility of plastic-reinforced concrete as part of 22.033 (Nuclear Systems Design Project), in which students were asked to pick their own project.

"They wanted to find ways to lower carbon dioxide emissions that weren't just, 'let's build nuclear reactors,'" Short says. "Concrete production is one of the largest sources of carbon dioxide, and they got to thinking, 'how could we attack that?' They looked through the literature, and then an idea crystallized."

The students learned that others have tried to introduce plastic into cement mixtures, but the plastic weakened the resulting concrete. Investigating further, they found evidence that exposing plastic to doses of gamma radiation makes the material's crystalline structure change in a way that the plastic becomes stronger, stiffer, and tougher. Would irradiating plastic actually work to strengthen concrete?

To answer that question, the students first obtained flakes of polyethylene terephthalate - plastic material used to make water and soda bottles - from a local recycling facility. Schaefer and Ortega manually sorted through the flakes to remove bits of metal and other debris. They then walked the plastic samples down to the basement of MIT's Building 8, which houses a cobalt-60 irradiator that emits gamma rays, a radiation source that is typically used commercially to decontaminate food.

"There's no residual radioactivity from this type of irradiation," Short says. "If you stuck something in a reactor and irradiated it with neutrons, it would come out radioactive. But gamma rays are a different kind of radiation that, under most circumstances, leave no trace of radiation."

The team exposed various batches of flakes to either a low or high dose of gamma rays. They then ground each batch of flakes into a powder and mixed the powders with a series of cement paste samples, each with traditional Portland cement powder and one of two common mineral additives: fly ash (a byproduct of coal combustion) and silica fume (a byproduct of silicon production). Each sample contained about 1.5 percent irradiated plastic.

Once the samples were mixed with water, the researchers poured the mixtures into cylindrical molds, allowed them to cure, removed the molds, and subjected the resulting concrete cylinders to compression tests. They measured the strength of each sample and compared it with similar samples made with regular, nonirradiated plastic, as well as with samples containing no plastic at all.

They found that, in general, samples with regular plastic were weaker than those without any plastic. The concrete with fly ash or silica fume was stronger than concrete made with just Portland cement. And the presence of irradiated plastic along with fly ash strengthened the concrete even further, increasing its strength by up to 15 percent compared with samples made just with Portland cement, particularly in samples with high-dose irradiated plastic.
The concrete road ahead
After the compression tests, the researchers went one step further, using various imaging techniques to examine the samples for clues as to why irradiated plastic yielded stronger concrete.

The team took their samples to Argonne National Laboratory and the Center for Materials Science and Engineering (CMSE) at MIT, where they analyzed them using X-ray diffraction, backscattered electron microscopy, and X-ray microtomography. The high-resolution images revealed that samples containing irradiated plastic, particularly at high doses, exhibited crystalline structures with more cross-linking, or molecular connections. In these samples, the crystalline structure also seemed to block pores within concrete, making the samples more dense and therefore stronger.

"At a nano-level, this irradiated plastic affects the crystallinity of concrete," Kupwade-Patil says. "The irradiated plastic has some reactivity, and when it mixes with Portland cement and fly ash, all three together give the magic formula, and you get stronger concrete."

"We have observed that within the parameters of our test program, the higher the irradiated dose, the higher the strength of concrete, so further research is needed to tailor the mixture and optimize the process with irradiation for the most effective results," Kupwade-Patil says. "The method has the potential to achieve sustainable solutions with improved performance for both structural and nonstructural applications."

Going forward, the team is planning to experiment with different types of plastics, along with various doses of gamma radiation, to determine their effects on concrete. For now, they have found that substituting about 1.5 percent of concrete with irradiated plastic can significantly improve its strength. While that may seem like a small fraction, Short says, implemented on a global scale, replacing even that amount of concrete could have a significant impact.

"Concrete produces about 4.5 percent of the world's carbon dioxide emissions," Short says. "Take out 1.5 percent of that, and you're already talking about 0.0675 percent of the world's carbon dioxide emissions. That's a huge amount of greenhouse gases in one fell swoop."

"This research is a perfect example of interdisciplinary multiteam work toward creative solutions, and represents a model educational experience," Büyüköztürk says.
This story has been updated to clarify that concrete containing both irradiated plastic and fly ash, rather than with irradiated plastic alone, is stronger, by up to 15 percent, compared to conventional concrete.

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MIT students fortify concrete by adding recycled plastic

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Discarded plastic bottles could one day be used to build stronger, more flexible concrete structures, from sidewalks and street barriers, to buildings and bridges, according to a new study.

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4D printing of polymeric materials for tissue and organ regeneration

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4D printing of polymeric materials for tissue and organ regeneration

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4D printing of polymeric materials for tissue and organ regeneration

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Dimming sunlight to slow global warming may harm crop yields: study.

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Dimming sunlight to slow global warming may harm crop yields: study.

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Infobase Learning
8 Aug. 2018

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How to become a space tourist: 8 companies (almost) ready to launch

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How to become a space tourist: 8 companies (almost) ready to launch

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On April 28, 2001, 60-year-old American businessman Dennis Tito became the first tourist to leave Earth's atmosphere behind, spending nearly 8 days in space, much of it aboard the International Space Station (ISS)-and reportedly paying $20 million dollars to do so. Despite objections from NASA, who thought that Tito's training would not be sufficient by the time of his flight-Tito also thinks it's likely they were concerned about his age-tourism company Space Adventures negotiated a deal with the Russian agency Roscosmos that got Tito a seat in a Soyuz.

Since then, there have been only six other space tourists, all traveling aboard a Soyuz to the ISS. The last one, Cirque du Soleil co-founder Guy Laliberté, flew in 2009. The end of this early space tourism era came about due to the doubling of the crew size aboard the ISS in 2009, which left no room for visitors on the station, as well as the retirement of the space shuttle in 2011, which meant that NASA needed all extra Soyuz seats to launch its astronauts.

But the seven space tourists won't be alone for long. Numerous private companies intend to launch their own space tourism programs. You've likely heard of the biggest players in the private spaceflight game: Sir Richard Branson's Virgin Galactic just resumed testing of its SpaceShipTwo vehicle earlier this month after a fatal test in 2014, and Blue Origin, Jeff Bezos' private spaceflight venture, is aiming to send crewed missions to space as early as this year.

And, in addition to these heavy hitters, there are quite a few other companies offering tourists a chance to reach space, too. Some are farther along in development than others, and there are always reasons to be skeptical when talking about space tourism. We've seen plenty of similar ventures come and go over the years without making it to space. But we choose to remain optimistic. Here are the most recent commercial space programs that would love to take you out of this world-for a price.

In early April, Orion Span announced its plans for the Aurora Station, billing it as the world's first luxury space hotel. Scheduled to begin construction in space in 2021 using the company's proprietary technology and construction methodology (though, what rocket system they'll use to launch the materials isn't yet clear), the station will have two private suites, with a total of four guests and two crew per stay. Guests will have to undergo a training program prior to their trip: "We have taken what was traditionally a 24-month training program to prepare travelers to visit a space station and streamlined it to three months," says Orion Span CEO Frank Bunger. "Phase one of the certification program is done online, making space travel easier than ever. The next portion will be completed in-person at Orion Span's state-of-the-art training facility in Houston, Texas. The final certification is completed during a traveler's stay on Aurora Station." In order to actually send guests to the Aurora Station, the company would like to partner with SpaceX for launches.

It will cost guests $9.5 million per person for a 12-day mission, making it one of the more "affordable" ways to temporarily live in space. "In context, historically, space tourists paid between $20 million and $50 million to stay aboard the ISS," says Bunger. "Our long-term goal is to continue to drive that cost down further so that space is more accessible to more people."

One other note-Aurora Station also plans on selling space condos if you want to make your stay a little more permanent.

Founded in 2004 by Sir Richard Branson, Virgin Galactic aims to take tourists on suborbital flights aboard its SpaceShipTwo spacecraft, which is launched from an aircraft rather than a rocket. Though the company hoped to complete its maiden voyage in 2009, a series of setbacks have continuously delayed that inaugural trip. The most severe of these was the 2014 loss of the VSS Enterprise during a test flight, which killed co-pilot Michael Alsbury.

The company just returned to testing on April 5 with a powered test of VSS Unity, which reached an altitude of 84,271 feet. The ship plans to eventually take people just to the edge of space, at about 330,000 feet. As SpaceShipTwo isn't designed for long-duration missions-total flight time will be just minutes-a seat on the vehicle for a suborbital flight will cost $250,000, and passengers won't need extensive training. As of 2017, about 650 people had purchased tickets.

Blue Origin's New Shepard program, named for America's first man in space, Alan Shepard, seeks to launch passengers in a capsule atop a rocket, just like in the Mercury, Gemini, and Apollo days. The program is still in development and the company is targeting late 2018 or early 2019 for their first flight with humans onboard.

The short-duration missions (lasting approximately 11 minutes) are expected to require a day of training, which would take place right before the flight. Training will include mission and vehicle overviews, safety briefings, and mission simulations. Tickets have not yet been released but are rumored to be comparable to other short-duration missions-i.e., in the low hundreds of thousands of dollars.

Responsible for organizing the launches of all seven space tourists, Space Adventures is the only truly successful space tourism company as of today. Though it hasn't been able to send new guests to the ISS since 2009 due to capacity issues, it is still promoting new missions, including a spacewalk at the ISS (no private citizen has ever performed one) and a trip around the moon, which would also include a stay at the ISS. While Space Adventures has no spacecraft of its own, it has long partnered with Roscosmos to send its guests into space via the Soyuz, and plans to do so in the future.

While its trips into space have been curtailed since 2009 and there is no firm timeline for re-starting them, the company is currently offering space-adjacent adventures, like trips to see a Soyuz launch, and flights in zero-g.

Historically, Roscosmos worked with Space Adventures to launch space tourists to the ISS, but it recently began development of its own program. The Russian agency plans on building a luxury space hotel module for the ISS through its partnership with RKK Energia, a space station contractor. Guests at the hotel will be treated to private living quarters with four "bedrooms" (each will be about 70 cubic feet), hygiene and medical facilities, as well as a lounge. Though its training plans haven't been released, it is expected to be an abbreviated version of the professional two-year program, similar to Dennis Tito's 8-day experience. Prices will range from $40 million for a one- to two-week stay to $60 million for a month-long stay that would include a guided spacewalk by a cosmonaut. The agency would like to launch the space hotel by 2022, though it should be noted that the ISS is scheduled to retire in 2028, meaning the hotel might be a short-lived endeavor.

In 2016, Roscosmos awarded private company KosmoKurs approval to build a reusable rocket with the intention of sending tourists into space. As only the designs have been approved, the company will likely have years of testing ahead of them before crewed missions will be launched. Similar to Blue Origin's flights, the short-duration missions (about 15 minutes long, with just a few minutes of weightlessness) will see guests launched in a capsule atop a rocket. The training program will last three days, and the entire package will cost approximately $200,000 to $250,000 per person.

Though its primary services are on-orbit research and manufacturing, Axiom Space's ultimate goal is to launch a commercial space station-a self-proclaimed successor to the ISS. Though the company hasn't released many details on its space tourism program, according to its website, it plans to send modules to the ISS by 2021 and establish its own space station by 2024. Private clients will be able to book seven- to ten-day missions to the station, and they will complete a several-week training program before the trip.

While Elon Musk's SpaceX is not a space tourism company-it currently operates cargo missions for NASA and other clients-it is developing technology for crewed missions aboard its Dragon spacecraft, which would typically carry NASA astronauts into space. But moving beyond its main operations, in 2017 the company announced its intentions to fly two private citizens on a circumlunar mission, following a similar plan to Apollo 8 (and the unintended flight path of Apollo 13). Details are scarce, but Musk recently announced that the prospective moon missions will not use Falcon Heavy rockets as planned, instead using a larger rocket in development called the BFR.

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How to become a space tourist: 8 companies (almost) ready to launch

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On April 28, 2001, 60-year-old American businessman Dennis Tito became the first tourist to leave Earth's atmosphere behind, spending nearly 8 days in space, much of it aboard the International Space Station (ISS)-and reportedly paying $20 million dollars to do so.

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American Institute for Economic Research
Veronique de Rugy
July 27, 2018

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For the second time since the last election, there's a growing effort to impose a carbon tax on Americans. Once again, this effort is being led not by the environmentalist left, but by conservative organizations and a small group of Republican legislators.

The timing is certainly interesting, given that the United States posted the largest year-over-year decline in greenhouse gas emissions of any advanced economy according to the International Energy Agency's annual survey of global carbon greenhouse gas (GHG) emissions and has now seen emissions fall for three consecutive years.

Unimpressed with the changes, a coalition - featuring some scholars at the American Enterprise Institute (where there is a vigorous internal debate over carbon taxes) and the R Street Institute - recently argued that conservatives and free market advocates should embrace carbon taxes if these taxes are used to replace existing regulations. These groups aren't the first to make that case.
One Tax for Another
When the Climate Leadership Council - which features veterans of past Republican administrations like former Secretary of State James Baker, former Treasury Secretary Hank Paulson, and economist Greg Mankiw - sought last year to convince newly sworn-in President Trump of the wisdom of a carbon tax, it made similar arguments.

It's worth noting how so much of the free market case for the tax has evolved over the years. It moved from a Pigouvian externality tax to reduce GHG to "desirable levels" to various versions of "Look at all the stuff we can do with the revenue from a carbon tax." First, there were calls for trading the carbon tax for the corporate income tax or other distortionary taxes. Then came the calls for trading the tax for lower regulations. Then there was the case for using the revenue for more spending on conservative pet programs like the Earned Income Tax Credit.

The latest proposal comes from Florida Republican Congressman Carlos Curbelo, who introduced a bill this week that would replace the gasoline tax with a carbon tax. It is notable as it happened in the tailwind of the House GOP overwhelmingly passing a nonbinding measure calling a carbon tax "detrimental" to the United States.

Curbelo's proposal isn't unique in that it too would trade in one tax for another. It shares another characteristic with the other "free market" proposals, one much less flattering. None of the proposals, whether taxes or regulations or subsidies, pretend to make any measurable difference on temperature reduction, which one would think is the primary goal. Writing about the Curbelo plan, AEI's Benjamin Zycher noted, "If we apply the EPA climate model to those emission cuts, the predicted temperature reduction at the end of the century would be 31 one-thousandths of one degree."
Tax as a Price
Now, assuming that an environmental policy is the goal, I can see why some free-market advocates might potentially find these carbon-tax proposals tempting. Among the range of typical political responses to real or perceived negative externalities, putting a price on them can seem like a market-friendly solution. In the absence of an owner of the atmosphere, the role of pricing carbon-emission externalities falls on the government.

Unfortunately, while these free-market advocates are fast to point to emission externalities, they are slow to recognize the externalities imposed by government interventions, the many risks outlined by public choice economists, and hence the important limitations to their approach.

The standard argument for the tax is that it is more efficient than the regulatory approach because it allows emitters to choose least-cost tools to achieve their mandated emissions reductions. There are problems with this standard textbook argument. For instance, it assumes that the emissions-reduction goal is exogenous - that is, that it is unaffected by the policy tools used to achieve it.

More importantly, there is a real knowledge problem in government that makes it practically difficult for legislators to determine the optimal GHG price. Then there is the fact that politicians are always revenue-hungry. It means that, even if they actually knew the optimal price for carbon emissions, they would have very strong incentives to jack up that tax rate well above the optimal price, making it counterproductive economically (and, by the way, also environmentally). The short time horizon of political decision-makers also means the revenue-maximizing rate in the short run is probably higher than that in the long run, causing added distortions.

Also, what happens if the tax is targeting the wrong thing? What happens if the tax doesn't yield the expected environmental results or is overly costly? Carbon-tax advocates don't seem to ask themselves these questions.

As Zycher wrote to me, "Beware of economists pretending to be politicians. The purported efficiency of a carbon tax is based upon the multiple assumptions that Congress will choose the optimal long-term tax rate, that the attendant environmental benefits would be both positive and worth more socially than the economic costs, and that such policies can be adjusted easily in the face of interest-group pressures to preserve them even given new economic and environmental information. Merely to state such premises is to refute them."
Piling Tax on Tax
Finally, raise your hand if you truly believe that swapping out regulations - or the gasoline tax, the corporate income tax, or other ill-advised policies - for a carbon tax will ever happen. Anyone? And raise your hand if you know of a way to make sure future Congresses will not simply reinstate the old taxes, if by some miracle the trade were to be successfully executed today. Anyone, anyone?

To understand the unicorn that the dream of a revenue-neutral carbon tax represents, just look at what progressives say on the issue. Consider David Roberts at Vox, who argues that a carbon tax would need to be "pretty damn high" to impact emissions, and that it's "irksome" that the focus is on revenue-neutral proposals in which "all the revenue is returned, none left for government spending." Environmental groups similarly opposed a 2016 carbon-tax initiative in the state of Washington because the revenue would have been used to reduce other taxes instead of to grow government. These guys at least have the merit of being either more realistic or honest.

The bottom line is that right-leaning carbon-tax advocates are pushing a compromise that the other side doesn't want and wouldn't find satisfactory. With this reality in mind, it is worth asking: with proposals that show no prospects of significant environmental improvements and carry the risks of massive economic downsides, why is it again that we should support this policy?

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By Veronique de Rugy | For the second time since the last election, there's a growing effort to impose a carbon tax on Americans. Once again, this effort is being led not by the environmentalist left, but by conservative organizations and a small group of Republican legislators.

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https://www.youtube.com/watch?v=7Q_Fu1KlVac