Bad Gone Blog

It may look like an ordinary USB memory stick, but a little gadget that can sequence DNA while plugged into your laptop could have far-reaching effects on medicine and genetic research.

The UK firm Oxford Nanopore built the device, called MinION, and claims it can sequence simple genomes – like those of some viruses and bacteria – in a matter of seconds. More complex genomes would take longer, but MinION could also be useful for obtaining quick results in sequencing DNA from cells in a biopsy to look for cancer, for example, or to determine the genetic identity of bone fragments at an archaeological dig.

The company demonstrated today at the Advances in Genome Biology and Technology (AGBT) conference in Marco Island, Florida, that MinION has sequenced a simple virus called Phi X, which contains 5000 genetic base pairs.

This is merely a proof of principle – “Phi X was the first DNA genome to be sequenced ever,” says Nick Loman, a bioinformatician at the Pallen research group at the University of Birmingham, UK, and author of the blog Pathogens: Genes and Genomes. But it shows for the first time that this technology works, he says. “If you can sequence this genome you should be able to sequence larger genomes.”

Oxford Nanopore is also building a larger device, GridION, for lab use. Both GridION and MinION operate using the same technology: DNA is added to a solution containing enzymes that bind to the end of each strand. When a current is applied across the solution these enzymes and DNA are drawn to hundreds of wells in a membrane at the bottom of the solution, each just 10 micrometres in diameter.

Within each well is a modified version of the protein alpha hemolysin (AHL), which has a hollow tube just 10 nanometres wide at its core. As the DNA is drawn to the pore the enzyme attaches itself to the AHL and begins to unzip the DNA, threading one strand of the double helix through the pore. The unique electrical characteristics of each base disrupt the current flowing through each pore, enough to determine which of the four bases is passing through it. Each disruption is read by the device, like a tickertape reader.

This approach has two key advantages over other sequencing techniques: first, the DNA does not need to be amplified – a time-consuming process that replicates the DNA in a sample to make it abundant enough to make a reliable measurement.

Second, the devices can sequence DNA strands as long as 10,000 bases continuously, whereas most other techniques require the DNA to be sheared into smaller fragments of at most a few hundred bases. This means that once they have been read they have to be painstakingly reassembled by software like pieces of a jigsaw. “We just read the entire thing in one go,” as with Phi X, says Clive Brown, Oxford Nanopore’s chief technology officer.

But Oxford Nanopore will face stiff competition. Jonathan Rothberg, a scientist and entrepreneur who founded rival firm 454 Life Sciences, also announced at the AGBT conference that his start-up company, Ion Torrent, will be launching a desktop sequencing machine. Dubbed the Ion Proton, it identifies bases by using transistors to detect hydrogen ions as they are given off during the polymerisation of DNA.

This device will be capable of sequencing a human genome in 2 hours for around $1000, Rothberg claims. Nanopores are an “elegant” technology, he says, but Ion Torrent already has a foot in the door. “As we saw last summer with the E. coli outbreak in Germany, people are already now using it,” he says.

By contrast, the MinION would take about 6 hours to complete a human genome, Brown claims, though the company plans to market the device for use in shorter sequencing tasks like identifying pathogens, or screening for genetic mutations that can increase risk of certain diseases. Each unit is expected to cost $900 when it goes on sale later this year.

“The biggest strength of nanopore sequencing is that it generates very long reads, which has been a limitation for most other technologies,” says Loman. If the costs, quality, ease of use and throughput can be brought in line with other instruments, it will be a “killer technology” for sequencing, he says.

As for clinical applications, David Rasko at the Institute for Genome Sciences at the University of Maryland in Baltimore, says the MinION could have huge benefits. “It may have serious implications for public health and it could really change the way we do medicine,” he says. “You can see every physician walking around the hospital with a pocketful of these things.” And it will likely increase the number of scientists generating sequencing data by making the technology cheaper and more accessible, he says.

As virtuous as you might feel when you choose organic foods sweetened with brown rice syrup instead of high-fructose corn syrup, you might actually be making a potentially toxic decision.

Infant formulas, cereal bars and other foods made with organic brown rice syrup are loaded with arsenic, found a new study. And while an occasional rice-sweetened energy bar probably won’t make much of a difference to your health, potential risks are greatest for babies, people with gluten intolerance and others who eat rice-heavy diets.

The findings suggest the need for regulations on arsenic in food, which so far, the United States Food and Drug Administration does not do.

“Here is just another food type that no one would consider would contain arsenic, and yet it does,” said Brian Jackson, an environmental chemist at Dartmouth College in Hanover, New Hampshire. “We really have no guidelines on what maximum levels should be for arsenic in food. Maybe it’s time this was considered.”

Arsenic, which is naturally ubiquitous in the environment and also a result of human activities, is a known carcinogen that, with enough daily exposure over years or decades, can also cause circulatory problems, type 2 diabetes, asthma and cardiovascular disease, among other ills.

The U.S. Environmental Protection Agency regulates exposure to the mineral, but only through public supplies of drinking water, which cannot contain more than 10 parts per billion of arsenic.

Only in the last couple of years have scientists realized that food, too, often contains arsenic. Studies have found the highest levels in fruit juices, rice and rice products, including crackers, rice milk and cereals made for both adults and babies.

At the supermarket one day, Jackson noticed two types of organic infant formulas that his team hadn’t yet tested in an ongoing study of arsenic in formulas, which had so far turned up only low levels. Results for both turned up levels measuring 20 to 30 times higher than previously tested varieties, and a look at their labels revealed the use of organic brown rice syrup in place of high-fructose corn syrup or other sources of sugar.

To follow up, Jackson and colleagues measured arsenic levels in 17 kinds of infant formula, 29 cereal bars, and three energy shots made for athletes, all bought from local supermarkets.

Of the two formulas made with organic brown rice syrup, one exceeded U.S. drinking water standards, the researchers report today in the journal Environmental Health Perspectives. That one was soy-based. A dairy-based, rice-containing variety came in right at those standards. Both exceeded the World Health Organization’s maximum tolerable daily intake level for infants. Formulas made without rice had much lower levels of arsenic.

Arsenic levels were also elevated in energy shots and cereal bars made with rice syrup, rice flakes, rice flour or grains of rice. Eating one bar at the top end of arsenic contamination would supply four micrograms of the mineral, Jackson said, or 40 percent of the limit set for drinking water. Commercially bought rice syrups had concentrations as high as four times greater than drinking water standards.

An estimated 20 percent of people in New England and 25 million people nationwide are already exposed to excessive amounts of arsenic from drinking water taken out of private, unregulated wells, said Joshua Hamilton, a toxicologist and arsenic expert at the Marine Biological Laboratory in Woods Hole, Mass. Many more are drinking public supplies of water that contain the maximum allowable level of 10 ppb.

As experts continue to debate exactly what levels of arsenic consumption are safe for people, the new findings point to the importance of considering food in addition to drinking water when adding up sources of exposure, Hamilton said. Added together, people might be getting too much.

Concerns are greatest for fetuses, babies and young children, for a variety of reasons. Young people eat and drink more for their size than adults do. They are more sensitive to all kinds of toxins. And studies show that arsenic exposure in the first 10 years of life is riskier than later on.

Many baby foods are made from rice, and scientists have yet to find any rice that doesn’t have arsenic in it, said Hamilton, who recommended that parents avoid feeding excessive amounts of rice-based products to their kids.

He also urged people not to panic, as rice also has health benefits, especially for people who can’t eat wheat or gluten. Arsenic does not accumulate in our bodies, like lead and mercury do. And it’s only chronic daily exposure that goes on for years that really matters.

“People shouldn’t freak out and think, ‘Oh, I had a cup of rice yesterday and something bad is going to happen,’” Hamilton said. “It doesn’t work that way, especially with arsenic.”

“This highlights how little we know about our food and what might be in there,” he added. “It’s something we should all pay more attention to.”

New nano-robots made from DNA can transport a precise deadly cargo to unhealthy cells.

The tiny robots bring closer the long-held nanotech dream of a fleet of small robots that can storm the body and kill diseased cells one by one.

“People already know about using antibodies to kill cells,” said Shawn Douglas, a technology fellow at Harvard Medical School’s Wyss Institute, which develops bio-inspired medical materials and devices. “The selective targeting and exposing the payload, that’s the big novel thing.”

Douglas and genetics research fellow Ido Bachelet made the new DNA nano-robots at Harvard with genetics professor George M. Church, known for helping to launch the Human Genome Project. Their research will appear in a forthcoming issue of the journal Science.

First, Bachelet and Douglas wondered if they could combine their respective expertise in immunology and building nanostructures to design a robot that would mimic the body’s immune system. It would recognize infected cells and push their self-destruct buttons.

Previous breakthroughs included a nanoscale cube with a lid debuted in 2009 that self-assembled in a process called “DNA origami.” Adding DNA strands caused the box to open. But Douglas felt that making the box so it got delivered to the right cells would be too difficult. So would making the mechanisms to enter and reprogram the bad cells.

Then Bachelet suggested that they didn’t have to reprogram anything. They just had to make a structure that could deliver the right antibodies to a cell’s surface with a clear message: stop dividing.

“We could actually make an open-ended container and then all it would need to do is just turn itself inside out,” Douglas said.

Their nano-robot is constructed from DNA in a clam shell shape held shut with a special DNA lock. That lock is designed to recognize certain kinds of cancer cells. When it encounters one, the robot springs open and exposes the antibody payload.

So, in the fight against cancer, these nano-robots could be the equivalent of sending SEAL Team Six.

“Our ability to perform that ‘surgical strike’ with nanoscale devices will ultimately allow us to do so in a way that’s safe for the patient,” Douglas said.

“Once we had the idea in mind that we don’t actually need to build some cage that gets inside the cell, we can actually just talk to the surface, we realized that all the other steps solved themselves.”

In the lab, their nano-robot successfully blew up lymphoma and leukemia cells, leaving good cells alone. Doing one of these reactions typically requires 100 billion copies of the robot. In order to start testing their creation on animals, the Harvard postdocs will have to figure out how to scale up to trillions.

Although the nano-robot works in a Petri dish, it will have to be redesigned for a trip through the bloodstream, Douglas said. Modifications are necessary to prevent the particle from getting cleared out by the kidneys or the liver before it has a chance to perform.

“My dream is for one of these devices to ultimately go through clinical trials and become an actual therapeutic that would be a novel treatment for some type of cancer,” Douglas said.

Kurt Gothelf is a professor of chemistry at Aarhus University in Denmark, and the director of the Danish National Research Foundation’s Center for DNA Nanotechnology. He and his colleagues made the self-assembling nanoscale DNA box with a lid in 2009.

“This is one of the things the field has needed, something to show that, hey, this can actually be useful” Gothelf said of the Harvard group’s DNA nano-robot. Although their smart nanodevice isn’t curing cancer yet, it does mark an important step along the way, he added.

“People have been talking a lot about robots that enter your body, and go to a place where something is wrong and fix it,” Gothelf said. “This is the first example that this might come true one day.”

Ancient giant eruptions in the Pacific Northwest may actually have been caused by the tearing of a titanic slab of rock and not the supervolcano underlying Yellowstone National Park, scientists now suggest.

Supervolcanoes are capable of eruptions dwarfing anything ever recorded by humanity. There are roughly a dozen supervolcanoes on Earth today, one of which sits beneath Yellowstone National Park.

Volcanism at Yellowstone is thought to have started with the Steens-Columbia River flood basalts. A flood basalt is the result of a large volcanic eruption that covers vast areas with lava, and the Steens–Columbia River flood basalts erupted more than 55,000 cubic miles (230,000 cubic kilometers) of molten rock over approximately 2 million years, spewing out more than 1 million times the notorious Mount St. Helens eruption in 1980.

Flood basalts are thought to typically occur when the head of a giant mushroom-shaped upwelling of hot rock rising from near the Earth’s core, known as a mantle plume,reaches the surface. Now researchers suggest a new way for these massive eruptions to form — a breach in a massive slab of the Earth’s crust.

Scientists generated computer models of how the complicated structure of the Earth’s mantle layer under the western United States evolved over the past 40 million years. They based their work on data from the USArray, a mobile seismic networkof 400 sensor stations traveling across the United States.

The researchers suggest that about 17 million years ago, a giant chunk of rock known as the Farallon slab that was diving underneath the western United States began ripping apart. This led to massive outpourings of magma, the pattern and timing of which appear consistent with the Steens–Columbia River flood basalts.

“When the slab is first opened, there’s a little tear, but because of the high pressure underneath, the material is able to force its way through the hole,” said researcher Dave Stegman, a geophysicist at the University of California, San Diego. “It’s like in the movies when a window breaks in an airplane that is at high altitude — since the cabin is at higher pressure, everything gets sucked out the window.”

Volcanoes are most often seen at the boundaries of tectonic plates. These new findings shed light on a way — in addition to mantle plumes — that volcanoes can emerge within tectonic plates, the researchers said.

“Only with a break of this scale inside the down-going slab can we reach the present-day geometry of mantle we see in the area,” said researcher Lijun Liu, a geophysicist also at UC San Diego. “Geochemical evidence from the Columbia River lavas can also be explained by our model.”

Mantle plumes, subducted slabs

Intriguingly, the supervolcano at Yellowstoneseems to be due to a mantle plume under the area, but the researchers do not think it was involved with the Steens–Columbia River flood basalts. “There are 40 to 50 active mantle plumes in the Earth right now, so just because one is close doesn’t mean that it was behind these flood basalts,” Stegman told OurAmazingPlanet. Still, he added, “we are now incorporating the Yellowstone plume into our modeling so we can learn a bit more about this region.”

Future research can also investigate the effects of slabs of rock diving underneath other tectonic plates.

“There are subducted tectonic plates, or slabs, underneath South America we’d want to understand better, and slabs underneath south Asia where there was a collision between India and Eurasia, and slabs underneath the Pacific Northwest, such as the Aleutians and central Alaska,” Stegman said.