If you’ve been wondering about 3-D printing, it’s probably for the same reason we are. On May 17, we learned that surgeons had placed a life-saving support — built on a 3-D printer — into the airway of Kaiba Gionfriddo.

Alejandro Roldan of the University of Wisconsin-Madison holds a printed, 3-D model of a heart against its computer design, which was based on a patient’s MRI scan. The system, still under development, could be used to guide surgery to repair defective organs. Using the realistic, printed model, the surgeon can perform “virtual surgery” to test the effect of heart-remodeling surgery on blood flow and pumping efficiency — without touching the patient.
Credit: The Why Files

Kaiba was an emergency case: Every day, his breathing stopped when his airway collapsed. The support was patterned on CT images of his airway, and printed in biodegradable plastic.

That welcome news came just three days after Forbes reported widespread interest in a handgun printed with similar technology.

A 3-D printer builds up objects layer by layer, using various methods to deposit and harden the “ink” where it is needed. Many materials, including plastic, metal, ceramic and even human cells, can now be printed, based on instructions from computer-assisted design (CAD) programs.

“Quite a few doctors said he had a good chance of not leaving the hospital alive,” says April Gionfriddo, about her son, Kaiba, who is now 20 months old. “We were desperate.”

With emergency clearance from the Food and Drug Administration, Glenn Green and Scott Hollister of the University of Michigan printed a tracheal splint, using a polymer that they expect to be absorbed by the body in three years.

On February 9, 2012, the splint was sewn around Kaiba’s airway to expand it and serve as a skeleton for proper growth. “It was amazing. As soon as the splint was put in, the lungs started going up and down for the first time and we knew he was going to be okay,” says Green.

How much hype? How much reality?

You’ve heard the 3-D hype: Factories are becoming obsolete. When you need a part, you’ll feed a downloaded file into your personal printer, and press “print.”

Today, many of those objects turn out to be trinkets, baubles, chess pieces or covers for slab-phones.

The situation reminds us of the giga-hype over nanotechnology about 25 years ago, when invisible, nanometer-sized robots would supposedly emulate proteins or enzymes and usher in the era of self-assembly.

The over-sell is not that bad, “but there’s still an incredible amount of hype” in 3-D printing, says Tim Osswald, a professor of mechanical engineering at University of Wisconsin-Madison. In fact, he says, some are touting — as a legitimate business venture — the idea of printing whole motorcycles. “No, we can’t do that,” he says.

“We can’t 3-D print clothing, though people say they will,” says Osswald, who researches the raw material — the “ink” — for 3-D printing. “Why should we? We can sew clothing much easier, and besides we don’t have a powder tiny enough to make a fabric.”

And still, as the printed airway and the handgun demonstrate, the 3-D printing wave is getting legs. What can — and can’t — these gadgets do? How do they work?

Promise and hype of 3-D printing

Some of the features of 3-D printing lend themselves to designing, prototyping, visualizing and experimenting. Others can make parts that cannot be made any other way.

3-D printing can:

• “Print” plastic, metal, even living cells. (After printing, ceramic and glass must undergo high-temperature firing).
• Eliminate the need for a mold, which is a major expense for metal, plastic, ceramic and glass parts.
• Create parts — even entire assemblies — that could never previously be made.

Building up the shape one layer at a time allows one part to be formed inside another. “It opens the ability to engineer in a different way,” says David Sheffler, in mechanical and aerospace engineering at the University of Virginia.

We wondered why we’re hearing so much about 3-D printing right now when a variant called stereolithography has been around for almost three decades. “It was used in the back rooms of design firms, and it always used to frustrate me,” says Hod Lipson of Cornell University. “I’d talk on the street about this incredible technology that could make anything you want, but nobody knew about it.”

A layer of powder on the work surface is selectively heated with a laser. The process called sintering solidifies the powder into the part; the unsintered powder can later be removed. Laser sintering allows low-volume production of complex parts in metal and plastic. Programming the laser light determines what becomes part, and what gets blown away to form voids.
Modified from Materialgeeza

Printing medical miracles

The life-saving replacement airway in Michigan is “a perfect example of different ways in which 3-D printing can be used to improve life,” says Lipson, co-author of a new book on the technology¹.

The technology is also infiltrating medicine, says Lipson. “There are hundreds of bone implants, printed in titanium, usually for hip replacements, based on an MRI scan.”

At Cornell, Lipson says, “We almost routinely print plastic bone for the veterinary school before a complex procedure, so the surgery is like putting a puzzle together the second time.”

3-D printing is also used in Invisalign plastic braces, which “have to be custom-made in a series that will gradually pull your teeth into the right place. Most people don’t know that 50,000 of these are 3-D printed each day. Someone you encountered today is wearing this 3-D printed prosthetic.”

3-D printing: the hard cell

3-D printing is not just for plastics. A “cell printer” that works like an ink-jet printer can spray a precise stream of gel containing living cells. Early tests are looking at using cell printing to form a meniscus, a tissue that cushions the knee.

Other simple tissues that may be printed include bone and cartilage, Lipson adds. “As the technology becomes more complex, the kidney, liver and spinal disks” are likely to be future targets.

Ideally, some replacement tissues should have the capacity to grow, Lipson says. “If a plastic heart valve was implanted in a child, it would have to be replaced” as the child matured. A valve made of the patient’s own cells might grow with the child, he says. “That’s revolutionary!”

Testing your mettle

Although 3-D printing began with plastic, metal can be printed in an inert environment that prevents oxidation. A laser sinters the metal powder after each layer is laid down. “The properties of the resulting metal are almost identical to bulk metal; it’s a very viable, engineering-tested way of making metal parts,” says Lipson.

But there’s little sense copying conventional metal parts, says Lipson, who points to growing interest in the aerospace industry for parts with new shapes. “What you made with a forge you can still make, but you can also make hollow or organic shapes, and end up with a shape with the same performance, but half the weight.”

Under consideration is 3-D printing of jet-engine turbine blades with air channels for better cooling.

A one-piece fútbol made with 3-D printing actually bounces on springy plastic internal struts. “Now engineering becomes open ended,” says Tim Osswald. “To make something like this with traditional molds, you would have to glue it together by hand. These are things that you could not make before. Now you can rethink engineering.”

Ball courtesy Tim Osswald/University of Wisconsin-Madison; video by The Why Files.

Aircraft are produced in small quantities, have very complex parts and can be very expensive. “That’s where the technology has the best value,” says Lipson. “You are not going to be printing toothbrushes.”

Mark Ganter, professor of mechanical engineering at the University of Washington, has come up with some interesting new printing materials, including ceramic. He is currently working on glass-ceramic composites, and says, “We see these being used in everything from armor to building materials. Disposable ceramic armor would be a big deal for a flak jacket; you could custom-tailor the inserts.”

3-D printing may also be used to print molds for casting metal — sidestepping the highly skilled job of mold-maker.

On the other hand…

After all this enthusiasm, it’s time for some cautions. For medium- and large-sized production runs of plastic parts, injection-molded plastic is cheap, fast, automated and reliable, even considering the cost of the mold.

Even the staunchest advocates warn that 3-D printing is not suited to every task, and issues concerning raw material, strength and deformation all need to be addressed as the field matures.

One issue is post-printing change of shape, “You get shrinkage, warpage, issues with dimensional stability,” says Osswald. “This has been a problem since plastic has existed. When Alexander Parkes made cellulose in 1856, a few months later, all the parts had warped because the plasticizer had evaporated.”

Printed plastic can shrink as much as 5 percent, Osswald says.

A second limitation concerns particle size in the “ink.” “We are using 50 to 100 micrometers now,” Osswald says, which creates the characteristic roughness on printed plastic, “but are hoping to get much smaller. We can make particles as small as 5 micrometers, but they still need to flow through the machine.”

Poor flow can leave voids in parts that become prone to cracking. In a tiny structure, Osswald says, pores and valleys become even more problematic. “You can get a mess, a part that will fall apart.”

Useful plastics, such as polylactic acid, a biodegradable substance used in medicine, can also be hard to powder, Osswald says. “You can freeze it and grind it into a very fine powder, but it’s very jaggedy, and does not flow easily.”

Tim Osswald holds a prototype “micropelletizer” that produces tiny pellets of new plastics. “We have made powders and are trying to scale up, making polymers that can’t now be made into spheres” for 3-D printing, he says.
Credit: The Why Files

How expensive? How cheap?

3-D printers have a long way to go before they can compete with injection-molded plastic, one of the cheapest technologies ever invented. But cost is falling, says Sheffler. “The cost of bigger printers is following Moore’s law [which predicted a geometric decline in the cost of computer memory] very closely. We bought one for $30,000 two years ago, and now it costs $20,000.”

When it was sold in 2011, the stripped-down MakerBot Cupcake CNC cost $455.
Courtesy: Bre Pettis

It’s the same trend evident in plasma TVs and many other new-fangled technologies, Sheffler adds.

A key advance came in the mid 2000s with the introduction of two open-source 3-D printers, says Lipson. “We went from a vicious cycle, where it was expensive, and therefore had a narrow market, and was therefore expensive, to an open-source, cheap, hackable system that anybody could use.”

Lipson, who helped usher “Fab@Home” into being in 2006, says it and another called RepRap, “seeded the transition, and since then hundreds, then thousands of 3-D printers were made… This has brought the technology to the attention of the masses, and the media.”

The airplane “would be incredibly complicated to build by hand, but we designed, engineered, did the analysis in a CAD program, and printed out exactly what we designed,” Sheffler says. “No manual labor was involved.”

And there’s a significant fringe benefit to 3-D printing, Sheffler says. “Students love it, and it’s not just students, it’s me. The students are out there doing real research, applications; we are learning as we go. It’s great stuff, we’re having a ball!”

This printed plane actually flies! A summer project for two students, the printed plane has a skin that takes the load. “There are no spars inside, it was fully printed,” says Sheffler. A standard battery-powered electric motor supplies the power. “This is a snap-together plastic airplane that’s very stable. We pulled off something amazing.”
Courtesy David Sheffler, University of Virginia

Osswald agrees. “Students are now thinking, ‘I can make this!’ They get weird ideas, ideas that we [older people] would not get because our brains are hard-wired. Young people can think outside the box, they don’t have the same restrictions that we have grown accustomed to.”

With 3-D printing, “There are a lot less restrictions on what you design.”

Summing up

So will a 3-D printer be fraternizing with your ink-jet printer in five years? Possibly… Prices are dropping, and capabilities are rising. But to really get the best from the printer, you my need some rare expertise, says Ganter. “The reality is that every one can own these things, but the difference is, to make an object on a 3-D printer, you need some kind of CAD background, you need skills that ordinary people don’t seem to possess.”

Researchers from Finland surveyed people around the globe who are involved in 3-D printing; 350 people responded.
Credit: The Why Files. Data from Statistical Studies of Peer Production.

And even though an increasing range of printer instructions is available for download, who knows if you will find data on the broken widget on your essential gadget? If not, as Ganter stresses, you may not have the computer-assisted design necessary to control the printer. “I tell my engineering students, you possess skills that the average person may not possess. It’s not that it’s impossible, but not everybody is an engineer, not everybody is a designer, not everybody is an artisan.”

To explore the swirling magnetic fields surrounding our neighborhood star, scientists have press-ganged a “dirty snowball” into an instrument of science.

As comet Lovejoy brushed perilously close to the sun, it was observed by instruments sensitive to extreme ultraviolet light. “EUV” is a short-wavelength, high-energy electromagnetic radiation that acts as the language of the corona, the turbulent, million-degree region surrounding our sun.

Lovejoy’s suicidal sojourn to within 140,00 kilometers of the sun occurred in December, 2011. As it passed through a fiery-hot region where artificial satellites may never visit, the comet was under the watchful eye of instruments on three satellites.

Although this was only the second comet ever observed in such high-energy ultraviolet light, “Sun grazing comets have been around for a long time,” says Cooper Downs, a solar physicist at Predictive Sciences in San Diego who was first author of the paper in this week’s Science. “This family of comets is thought to have come from something that broke apart about fifteen hundred years ago.”

Before its solar roasting, Lovejoy was probably a few hundred meters across, composed mainly of ice.

As you can see from the video, the comet’s tail seems to be buffeted by an invisible wind. In reality, that wind is the sun’s intricate magnetic field.

Solar magnetism

As the icy comet cruised through the super-hot corona, it sublimated into gaseous water, which three seconds later separated into oxygen and hydrogen under intense radiation. The oxygen atoms immediately lost electrons and became ions, forming the state of matter called plasma.

Because plasma is electrically charged, it responds to magnetic fields.

The hot plasma also creates the EUV radiation that was “seen” by the satellite instruments dedicated to observing the sun. These detectors are tuned to EUV because the star’s intense magnetism and radiation elevate conditions to 1 million degrees C, creating a bountiful source of this high-energy radiation.

EUV, says Downs, “is the natural ballpark for observing the corona, plasma, and the arching magnetic structures” near the sun. “The Solar Dynamic Observatory sits and stares, making a continuous image, at these wavelengths.”

When a July, 2011 comet cruised by the sun, it was “a happenstance that it showed up in EUV,” says Downs. “This led the operators of SDO to off-point the satellite to catch Lovejoy’s ingress in December 2011, which was a big deal because it was an interruption of the standard SDO observing program.”

The pay dirt in the Science study, the fact that the tail would respond to the magnetic field, “was unexpected,” Downs says. But by responding to the magnetic field and sending out ultraviolet messages, plasma in the comet’s tail became a magnetic-field detector.

Modified from original graphic by Kelvinsong

The sun isn’t just a ball of hydrogen and helium.
Solar prominence: A filament of dense, relatively cool gas shaped by closed magnetic fields.
Solar flare: Sudden release of energetic mass of ions and atoms, often leading to a coronal mass ejection that can spit this material past Earth’s orbit.
Photosphere: Visible surface of sun, source of most of the visible light.
Corona: Super-hot gas and plasma surrounding the star.
Core: generates almost all of Sun’s energy by fusion
Radiation zone: energy is transferred out mainly by radiative diffusion
Convection zone: energy is transferred out mainly by convection

Sun: Hottest act in town!

Earth has its strong points, but it’s the sun that dominates our tiny corner of the universe. Beyond the torrent of visible and invisible radiation, the sun also emits a solar wind of charged particles, spits out the occasional mass of hot atoms, and is surrounded by a phenomenal, changing magnetic field.

The magnetic field originates in a dynamo — rotation of magnetic materials — inside the sun.

The comet’s tail responds to both open and closed magnetic fields, Downs says. The complex, closed fields loop back to the sun, while the open fields are the energy driving the solar wind. “As the plasma streams out, the field is carried out with it, and the wind buffets Earth.”

The wind can interfere with electric lines, radio transmissions and satellites.

The outer extent of the solar wind, far beyond Pluto, defines the boundary between the heliosphere, dominated by the sun, and galactic space, says Downs.

So what?

The study was the first observation of the wiggle in a comet’s tail this far down in the solar atmosphere, says Downs. “It tells us about what happens to the comet as it begins to feel the magnetic field, becomes part of the magnetic field.”

And so Lovejoy was converted into a disposable scientific instrument, yielding data from a zone that spacecraft almost certainly will never enter.

None of this will help poor old Lovejoy. The little comet nearly survived its attempted suicide, but instead gave its all in the name of science. “Everyone expected it to disappear, because it came so close.” The comet was seen leaving the sun, says Downs, “which was surprising, although it soon fragmented as the thermal stress worked its way into the core.”

By Dec. 19, Lovejoy’s corpse had disappeared, Downs adds. Mission accomplished!

Photo, fair use: Copyright held by the film company or the artist.

Angelina Jolie as Lara Croft: Tomb Raider. The movie was a smash-hit adaptation from a video game.

On May 14, cinema super-star Angelina Jolie announced that she’d had a double mastectomy to prevent the family scourge of breast cancer. With a courageous and medically explicit discussion of her odds and her “medical choice” to remove both breasts, Jolie splashed the issues of cancer prevention and genetic testing for cancer across the front pages.

Jolie explained her decision in the New York Times:

About 10 percent of breast cancers have a genetic component, and two mutations, called BRCA1 and BRCA2, greatly increase the lifetime risk of breast, uterine and other cancers.

The BRCA genes normally suppress tumors by repairing broken DNA; when the gene is mutated, both suppression and repair may fail. By itself, the BRCA1 mutation raises the lifetime odds of breast cancer to about 65 percent, about five times the U.S. average. The odds are higher if, as in Jolie’s case, many relatives have the cancer.

No longer behind the curtain

Photo: Jeffrey Smith

Jim Janetski holds his bass guitar close to see the strings. Blinded by an accident long ago, he can see faintly. Janetski, who has struggled with colon cancer for much of his life, says, “I love music, it’s helped me through my cancer a lot more than I ever thought.” Colon cancer, and early-onset tumors, are often hereditary.

Just as First Lady Betty Ford’s open discussion of her mastectomy in 1974 brought sunshine to the issue of breast cancer, Jolie’s announcement has fueled discussion of genetic testing and preventative surgery. “Our calls have quadrupled in the last week,” says Suzanne Mahon, a professor of hematology and oncology at the hereditary cancer program at Saint Louis University. “Angelina Jolie … is high profile, and has definitely raised awareness among patients and the community: ‘Is genetic testing something I should consider?’ It begins the conversation about what it means to be a carrier for a gene for cancer predisposition.”

Mahon appeared on radio and television May 14, and had scheduled 67 patients by May 29, about four times the usual rate. Much of the interest has been among women, but the focus goes beyond BRCA. Mahon says many callers knew they had a risk (she had previously tested their relatives), but still had not phoned for an appointment. “Jolie’s announcement gave them the bump to make the call,” Mahon says. “That’s all good.”

In many cases, Mahon says, people who are worried about breast cancer “should actually be worried about another hereditary cancer syndrome. When they give us their history, it may be that colon or another cancer is most relevant.”

Unusual actress, unusual patient

Just as Jolie has played unusual women in her movies, it’s critical to remember that her medical situation is not usual. Carrying the BRCA1 mutation, and having multiple relatives with breast cancer, she said she had 87 percent lifetime odds of breast cancer. Because BRCA1 can affect other organs, she also had a 50 percent chance of ovarian cancer, which she plans to prevent by ovary-removal surgery.

Photo: NIDCC

A researcher at the National Institute on Deafness and Other Communication Disorders provides a genetic counseling session.

The discussion of genetics and preventive surgery reflects medical progress and changing social norms, says Victoria Raymond, a certified genetic counselor at the University of Michigan Cancer Genetics Clinic. Preventive surgery “is becoming more mainstream because we are more open about discussing the options. Saying ‘breast’ 20 years ago was taboo. It’s more a conversation to have today.”

How would a genetic counselor deal with a patient who, like Jolie, faced scary odds of getting cancer? “When we counsel women,” Raymond says, “we try to get a feel for what they need to do to feel more comfortable, to take control of the risk. Some women cannot fathom doing the surgery. They say, ‘Let’s stick with surveillance.’ Some say, ‘I cannot sleep at night, cancer is all I can think about.’”

“I don’t think a double mastectomy in this case is radical, but it’s not for everyone,” Raymond says.

Jolie had other options, including early detection through intensified screening with MRI and mammograms, or perhaps drugs that could abate the risk of breast cancer (but not as well as mastectomy). Although cost is no object for a rich movie star, we don’t know whether insurance plans would cover prophylactic removal of the breasts, followed by reconstructive surgery.

Who should get tested

As we’ve seen, seeking genetic counseling can be frightful, but it can have benefits even without testing, says Jessica Joines, a certified genetic counselor who specializes in breast and ovarian cancer at the University of Maryland school of medicine. “One of the biggest misconceptions is that meeting a genetic counselor means you are necessarily going to go down the road of testing. We are here to help discuss the pros and cons, and help the patient make the decision on whether genetic testing is right.”

The meeting can be valuable in either case, says Joines. “We do a very thorough risk assessment, based on the personal and family history, and the risk factors for the cancer in question. Sometimes women with a family history may overestimate the likelihood that they carry a mutation.”

Even before genetic testing begins, Raymond encourages women to think about how they would use the results. “That’s how we want to use genetics: How is it going to change how we take care of someone?”

Getting testing

With Jolie in the headlines, some people may wonder about saving money by ordering genetic tests over the Internet, but that’s not a smart way to test for a serious disease, Mahon says. “Unfortunately the wrong tests get ordered. It’s an emotionally laden situation, and people really should have counseling with a trained, credentialed genetic counselor.”

In 2006, the Government Accountability Office found that “direct to consumer” genetic tests were misleading.

An informed approach to genetic testing must assess the risks and benefits, and explore insurance issues like preauthorization and coverage, and results are best presented in person, Mahon says. “If the result are positive, we schedule 90 minutes, even multiple appointments” to discuss the results.

Once a mutation is detected, relatives, depending on their relationship to the patient, may need to consider counseling and testing, Mahon says. “And there are questions about insurance discrimination. Do you need to up your life insurance? There is a whole host of issues.”

Federal law prohibits insurance and employment discrimination based on a genetic test.

Definitive? Not always…

Although Jolie’s case was pretty clear-cut, genetic testing does not always give definitive results. Many patterns of hereditary disease, for example, have not been tracked to specific genes. “One of the biggest challenges, when you are working with a family who you feel does have a hereditary component to cancer, is when you do all this testing, and the result comes back negative,” says Joines.

Plenty of gray areas exist, even with the well-known BRCA genes. Not every woman with a harmful BRCA1 or BRCA2 mutation will develop breast and/or ovarian cancer, and not every cancer in these families is linked to these mutations.

Even a failure to find a genetic abnormality can be confusing. “It takes a lot of education, counseling, to convey that the negative result does not mean there is nothing to worry about, that there is not something genetic in the family,” Joines adds. “There are causes we don’t know. Probably one-third of hereditary breast cancers are due to rare or unknown genes.”

Even a field as number-rich as genetics can stumble when it comes time to say, “You have X percent lifetime chance of getting cancer Y.” Variations in individual lifestyle, environment and other genes can all play a role, and so it can be difficult “to give one absolute risk number,” Joines adds. “A lot of times, we give a range for the number; we feel that’s most accurate. Inherent in genetic testing is a certain amount of uncertainty. You have to make a decision on percentage chances, and you need to be comfortable with the decision.”

Genetic testing: treatment aid?

The BRCA1 mutation that caused Angelina Jolie to choose surgery resides in reproductive cells. Because it is copied into every tissue, people carrying the mutation are prone to cancer in several tissues. But in the vast majority of human tumors, the genetic abnormality is local — due, perhaps, to radiation, chemical assault or spontaneous mutation.

In glioblastoma, the most common and aggressive brain cancer, three percent of cases result from a genetic abnormality called gene fusion, says Antonio Iavarone, a professor of pathology and neurology at Columbia University.

Gene fusion means just what it says: Two genes splice together and start producing a deadly protein.

When Iavarone injected the fusion gene into mice, “100 percent of those mice get very aggressive brain tumors,” he says. “The fusion gene [working through the fusion protein] causes the cancer.”

Last year, Iavarone reported¹ that drugs that interfere with the fusion protein dramatically slowed the growth of glioblastomas in mice.

“The possibility to treat patients who were selected for the presence of the fusion gene was there since the first moment,” Iavarone says. “After our work was published, I was hoping that a clinical trial would follow very rapidly. But these drugs would only work for patients who have the fusion gene; it does not makes sense to give the drugs to other patients, so the first step is to screen … for that three percent.”

A new view of clinical trials

A simple DNA test could identify the fused genes, he says. “We know how to block the activity of this protein with drugs that are already available [although not approved for marketing] from pharmaceutical companies.” Unfortunately, he says, drug companies want to forego screening and give the candidate drug to everybody in the trial, but that is a recipe for failure. “The vast majority of patient will not benefit.”

And so a clinical trial has not begun, Iavarone says.

Because the same gene fusion occurs in other cancers, Iavarone says it no longer makes sense to automatically categorize cancers by their source organ. Ideally, “You don’t treat tumors because of where they originate, but based on their molecular content, the genetic alterations.”

Eventually, Iavarone says, “Breast tumors may be treated exactly like tumors from the brain, as long as they have the same genetic alterations. This is really the genomic revolution in cancer research: using new sequencing technology to understand which patient can benefit from a certain drug.”

Ever since 2003, when the first human genome was decoded, we’ve been waiting for the health benefits touted by supporters of the $3-billion genome project. Finally, Iavarone says, all the knowledge and equipment stimulated by that project are starting to pay practical benefits.

Jolie’s public decision, Iavarone says, “Underscores the possibility of preventing cancer by using genomic knowledge. In brain tumors, and unfortunately for the vast majority of cancers, we don’t have the opportunity, there is no germ-line mutation, we can’t say you are at risk. But we are starting to see treatments, and that is another opportunity raised by genomic knowledge.”

About 30 years ago, many cockroach haters began to use baited traps that blended high-fructose corn syrup with insecticide. But within seven or eight years, the traps started losing their clout.

“We first assumed that cockroaches were becoming resistant to insecticide, “says Coby Schal, a professor of entomology at North Carolina State University. “That’s been discovered in more than 1,000 species.”

Upon a closer look, scientists found that the roaches were turning up their noses at glucose, a primary component in the cheap corn syrup that was used to attract roaches to the poisonous bait.

This week, Schal publishes an explanation for the change: a mutation in German cockroaches that alters taste-sensitive nerve cells. The mutation causes these cells to perceive glucose as bitter, not sweet, so the mutated roaches, no dummies, disdain bait containing glucose.

The German cockroach Blattella germanica is small and ubiquitous in buildings. “It does not have a natural world,” Schal says. “You can’t find them outside human structures,” such as barns, restaurants, schools, and especially homes.

Three cheers for glucose!

Normally, animals love glucose, not hate it, Schal says. “It’s no wonder that plants put glucose and fructose [another simple sugar] into nectar, so insects will pollenate them.”

But bitter trumps sweet, because bitter compounds are often toxic. “This makes a lot of sense,” Schal adds. “If you taste something bitter that could kill you, it would make sense to ignore any sweet taste.”

To determine why these roaches shun glucose, Schal, Jules Silverman and Ayako Wada-Katsumata made electrical measurements of sensory hairs near the mouth, which contain neural cells variously attuned to sugar, bitter, water or salt. “We put an electrode over the top of the hair and recorded the neural responses,” says Schal. Because each type of nerve cell gives a typical impulse, it was possible to distinguish the firing of sugar cells.

Among glucose-averse roaches, Schal found, a mutation placed a glucose receptor on the bitter neuron, giving sugar the bitter taste that’s obvious in the movie.

Loathing glucose aids survival, but only when the sugar comes with a dollop of insecticide, Schal says. Otherwise, “this cockroach would be at a huge selective disadvantage, as they would not have access to the calorie-rich diet” that cockroaches crave.

“To the German cockroach,” he says, “that Krispy Kreme donut on the counter is a bonanza, but if it evolves this behavior, it can’t touch that Krispy Kreme.”

Cockroaches: just disgusting, or dangerous too??

Our innate disgust of cockroaches is more than creepy-crawlies paranoia; these arthropods can harm us via allergies and infectious disease.

Disease Transmission

Cockroaches can ferry pathogens from their filthy habitat into your kitchen. They also ingest microbes while grooming, says Schal. “We have shown that the digestive tract of the cockroach contains microbes that represent the environment it lives in.”

Allergies

As a cockroach sheds feces, saliva, eggs and exoskeleton into the environment, those bits can trigger allergic asthma. In the United States:

* 26 percent of the population is allergic to the German cockroach;

* 63 percent of homes contain cockroach allergens; and

* 44 percent of living room floors have cockroach allergens.

Data: Environmental Health Perspectives, 114(4), 522.

Sweet is beautiful — or not…

While mutations usually destroy specific functions, Schal notes, the cockroach mutation actually confers a new ability. “Normally, the gene is non-functional, but in this case the roach hasn’t lost its sweet tooth, it’s gained a bitter tooth for glucose.”

At the same time, the roaches’ sweet receptors become less reactive to glucose. “It’s a two-step whammy,” says Schal. “They now respond to glucose as bitter, and there is a suppression of the response to glucose as sweet.”

This flexibility is another reason to respect roaches, says Schal. “I have been working with them for 30 years, mostly involving the arms race between roaches and us. We lob something at them, and they lob something twice as big back at us.”

The roach’s rapid response to the new baiting strategy is sobering, says Walter Goodman, a professor of entomology at the University of Wisconsin-Madison. “We have not been using baits all that long. The strong selective pressures put on the wild-type roach have led to resistance via the antennal neurons in less than 50 years (possibly 200 generations).”

Although the result may look like learning — after all, the roaches have changed their behavior to survive their new environment, “There is no learning involved,” Goodman says. “The change is in the antenna receptors, not in the brain.”

And these mutations are making some baits obsolete, Goodman adds.

Replacing glucose with another sugar could reinvigorate roach traps, Schal says. “But fructose is very expensive, and maltose is used in beer. Cockroaches love maltose, but we don’t want them competing with beer-makers.”

In 1952, the Toms River Chemical Plant opened a vast factory in rural New Jersey, dedicated to making dyes based on a coal product, anthraquinone. Prized for bright, color-fast colors, the manufacturing process also produced prodigious streams of toxic waste.

As the plant, eventually renamed Ciba after its owner, the Swiss chemical giant, prospered, streams of waste filtered into the sandy soil and reached the Atlantic through a leaky pipe. Less obvious at the time, a field of municipal water wells a mile or so from the plant fence were contaminated by midnight dumping of barrels of toxic trash from chemical giant Union Carbide.

You might guess the outcome: A cancer cluster, a town divided against itself, a massive struggle pitting people who felt victimized against a truculent, entrenched corporation. Caught in the middle: state and federal regulators.

Toms River details the decade-long effort to unravel and repair the environmental damage left by the Ciba plant, which closed in 1996. It explores the 1856 discovery of a bright purple residue that “clung flawlessly to a cotton cloth,” and the rise of the Swiss chemical industry, together with its constant need to dispose of toxic byproducts.

In parallel, author Dan Fagin describes the fitful progress of toxicology and epidemiology — disciplines that were tested so strongly at Toms River.

In 1700, for example, the Italian physician Ramazzini published Diseases of Workers, based on his visits to workplaces, which “included startlingly accurate descriptions of diseases associated with fifty-two occupations, from lead poisoning of potters and mercury poisoning of mirror makers to the hunched spines and overtaxed minds of sedentary ‘learned men.’”

The signature ailment at Toms River, childhood leukemia, afflicted families living near the plant. Repeated investigations of this “cancer cluster,” however, could not quite pin down the source. Although there was obvious aquifer pollution, nobody had stored samples of past drinking water, so it was impossible to know how much poison they contained.

And here is the result, as Fagin describes it: “By the late 1980s, there was no avoiding the unsetting conclusion: [Investigating] neighborhood cancer clusters appeared to be a fool’s errand, and a source of perpetual embarrassment to the agencies that conducted them and the politicians who had to defend their unsatisfying results.”

Toms River the book is anything but unsatisfying. Fagin weaves — without a bit of maudlin grandstanding — strands of chemical invention, corporate behavior, dedicated doctors, nurses and especially citizens, family tragedy, and the invention of epidemiology.
The result is a stunning achievement: A historical-scientific page turner, all fact, all the time!

Photo: J Telling

Gas bubbles from briny water emerging from the floor of a deep mine. The water’s chemical composition could feed microbes, if any are living here, 2.4 kilometers underground.

Water gushing from a deep mine in Ontario has been isolated from the surface for more than a billion years, a Canadian-United Kingdom scientific group reported today. Intriguingly, the water contains hydrogen and methane, which support bacteria and bigger organisms in the ocean depths, another location where sunlight, life’s usual source of energy, is unknown.

Several analyses indicate that the mine water has been underground for 1.5 to 2.5 billion years, more or less.

Tests for bacteria in the Ontario samples are not complete, but scientists have already found microbes trapped for millions of years in a South African gold mine.

The new study could expand the size and age of the immense bacterial realm beneath our feet, and could even help justify the search for life inside Mars, where geologically quiet regions may retain the liquid water that dominated the planet’s surface billions of years ago.

In deducing how long the water has been isolated from the surface, the researchers focused on inert gases like helium, xenon and argon, which abstain from chemical reactions.

The isotopes of an element are chemically identical but have different physical properties, such as mass. Particular isotopes can only come from a limited number of sources, and do not undergo radioactive decay.

The ultimate source of helium-4 is uranium, and measuring helium-4 can produce an age for the fluid, says project leader Chris Ballentine of the University of Manchester. “We know the concentration of uranium in these rocks, and can calculate that it would take X number of years for this level of helium-4 to build up.”

The researchers calculated that the accumulation of helium-4 would require about 1.14 billion years. Argon-40, another stable isotope, derived from potassium, would require 1.5 billion years. Those dates could be off by hundreds of millions of years in either direction.

Three xenon isotopes provided data on isolation from the surface. “Other workers have been looking at how the xenon isotope composition in the atmosphere has evolved,” says Ballentine. “A small amount of the atmosphere is dissolved in water when it is last at the surface, and when the water percolates into the ground, it takes that signature with it.”

The final step is to match the xenon concentration in the underground water to a time when the same concentration was present in the atmosphere; this process yielded an age of about 1.5 billion years.

Answering the “so-what?” question

The study gives a new view of how water behaves deep underground, says Ballentine, who studies fluid migration. Knowing how fluids form and move will, for example, shed light on what may happen if carbon dioxide gas is pumped underground to reduce greenhouse gas pollution.

Although the ancient water contains methane and hydrogen, which support bacteria in some locations, the “million dollar question” remains to be answered, Ballentine says. Nobody yet knows whether life is present in the water from the Ontario mine. Still, he adds, “We have found an environment that can host life, support it and nurture it for hundreds of millions, or billions of years.”

Because the ancient rock in the Ontario mine is located on the Canadian Shield, where earthquakes and volcanism are absent, “the most important implication is the extent of time that these environments can support life… without being disrupted.”

It’s almost certain that similar locations exist elsewhere, Ballentine adds. “Eventually we hope to find a spectrum of ages that would allow us to … start building a far better understanding of how life finds these pockets, evolves in them, and survives in them.”

Admittedly, that statement is premised on a big “if.” As Ballentine concedes, “We don’t know if there is there life down there, or even what it would look like.”

We may call this the age of information, but we could also call it the age of steel. More than 1.5 billion tons of steel are made each year for bridges, concrete reinforcement, vehicles and building frameworks, among many other purposes.

Photo: Wikimedia Commons

The Hulme Arch Bridge, at Hulme, Manchester, England, is a harmonious construction of steel cables and arches.

Steel is usually about 99 percent iron, and the tight bond between iron and oxygen in iron ore explains much of the environmental cost of making steel.

Now MIT professor Donald Sadoway has found a way to sidestep many of these drawbacks with a 1565° C process that uses electricity to separate iron and oxygen.

A backward battery

Electrolysis is the reverse of a battery. Both batteries and electrolytic cells contain an electrolyte that conducts electricity between two electrodes. In both cases, the process alters the chemistry of the electrolyte, and an electrical current flows.

In a battery, chemical energy in the electrolyte is converted to electrical energy. In electrolysis, electrical energy is converted into chemical energy.

In iron electrolysis, reduction — the chemical reaction that allows iron to release oxygen — occurs at an electrode called the anode. Nearly pure iron pools at the other electrode.

In conventional iron smelting, the oxygen reacts with carbon in coke, a carbon fuel, to make carbon dioxide. The molten iron is brittle, due to a high carbon content, so a second step is needed to drive off that carbon.

Both processes make carbon dioxide pollution.

Coke, a fuel used to strip oxygen from iron ore, was made in this English coke oven. Rollover to see air being blown through molten iron to clear carbon leftover from the coke. This Bessemer process is no longer used, but impurities remain a hindrance in steelmaking.

Credit 1: Earthwatcher, (rollover) 2: Republic Steel, Youngstown, Ohio, Wikimedia Commons

Because the energy to cut the bond between iron and oxygen — and much of the electricity used to refine steel — both originate in coal, the iron and steel sector is “the second-largest industrial user of energy … and the largest industrial source of CO₂ emissions,” according to the International Energy Agency.

By improving efficiency, the new process should cut down on greenhouse gases. However, although because electricity is still needed, the size of the benefit depends on how the current is generated.

Still, the process can, judo-style, convert the oxygen in iron ore from a liability into an asset. “Oxygen bubbles float to the top, and you can collect them,” says Sadoway. “You are making, for every ton of iron, two-thirds of a ton of oxygen that’s industrial quality, marketable.”

Amazing anode

The critical advance is an anode made of chromium and iron that can survive a 2850°F, oxygen-rich process — conditions conducive to a chemical reaction that would obliterate most materials.

Instead, a thin film of metal oxide forms on the anode in the intense heat. “It’s remarkable,” says Sadoway. The oxide, he says, “forms a protective layer that prevents further consumption of the base metal — yet at the same time, is not resistive to any great extent.”

That allows an electric current to enter the hot brew of iron oxide.

Hurdles remain. “I am not saying anybody will take a wrecking ball to an integrated steel plant,” Sadoway says. But he thinks an electrolytic smelter could avoid the need for a sinter plant to process iron ore, a coke oven to produce coke, and an oxygen furnace to remove excess carbon left over from the coke.

Photo: Shutterstock

Huge tonnages of steel reinforcing rods are used to strengthen concrete.

Steel plants cost billions of dollars, and must produce a couple of million tons per year to make money, Sadoway says. If the electrolytic process, with its reduced need for fossil fuel and equipment, survives further testing, smaller plant expansions could be possible, he says.

Any climate-based restrictions on carbon dioxide pollution will only help the new process become a player in the giant steel industry, Sadoway says. “We are hoping there will be early adopters,” he says, “if the price point is lower and there is an environmental imperative toward clean steelmaking.”

A field of volcanoes you have never heard of will wake up, and if it fulfills its geologic potential, the consequences will be heard around the world.

Curiously, Laguna del Maule, situated along the spine of the Andes, doesn’t even look like a volcano. No towering peak, no plume of smoke or steam, no stench of sulfur. But 36 times in the past 20,000 years, volcanic vents surrounding the lake basin have created monster fields of lava — with huge deposits of volcanic glass, pumice and ash.

Once, almost a million years ago, this volcano field had an eruption that, if repeated, could change history by affecting air travel, agriculture and climate. Tantalizing scraps of lava indicate enormous eruptions 1.5 million and 336,000 years ago.

It’s a maxim of geology: What happened before can happen again.

The volcanic field is 20 kilometers in diameter, and the recent surge in attention is largely due to a widespread, 1.5 meter rise since 2007. “That’s phenomenal,” says Brad Singer, a professor of geoscience at the University of Wisconsin-Madison, who began studying this part of the Andes 20 years ago. “There is no other volcano in the world that is going up at this rate.”

Other causes for concern include swarms of earthquakes, horizontal spreading, spreading faults, and new detections of carbon dioxide gas that likely signal the enlargement of the underground magma pool that powers the volcano.

Eruptions can be ranked by estimating the volume of volcanic ash (mainly tiny shards of glass) they release. In 1980, Mt. St. Helens released about one cubic kilometer. In 1991, Pinatubo in the Philippines sent more than 10 cubic kilometers; its ash and sulfur gas injected into the upper atmosphere cooled the planet for two years.

About 950,000 years ago, an eruption at Laguna del Maule spewed dozens of cubic kilometers — perhaps more than 100. The eruption blanketed Argentina, downwind, with ash.

Based on data from Geological Society of London, 2005 and Gunder and Mahood, 1988. Graphs by The Why Files

The bigger the eruption, the less common it is. Laguna del Maule could go back to sleep, or (rollover) enter the history books as the largest eruption in recorded history.

Past is prologue

A 100 cubic-kilometer eruption could cause global cooling, and intense damage to agriculture could affect the entire globe.

Because the only people around Laguna del Maule are the horsemen who drive cattle in the summer, the immediate human impacts will be limited — unless giant flows of hot rock or debris reach Chilean cities. But dense ash-fall during the growing season could devastate agriculture in Argentina, to the east.

Just 50 kilometers north of Laguna del Maule, a similar volcanic field, called Calabozos, has had three super-eruptions in the past million years, spewing about 1,000 cubic kilometers of ash in total.

Those eruptions rank among the largest in a million years.

The Why Files

Laguna del Maule, a massive volcanic complex in Chile, could change the planet, with an eruption like three giants at nearby Calabozos. Maule could be returning to life. How dangerous is that?

The immediate cause of concern at Laguna del Maule comes from radar satellites and the global positioning system, which show that 1.5-meter rise in six years. The accelerating uplift is almost certainly due to new magma entering a pool located five kilometers underground.

In 2013, with support from the National Science Foundation, UW-Madison geoscientists began a field campaign to gather more basic data on Laguna del Maule.

“Our aim is to try to figure out if magma is actively intruding in the crust below the volcanic field,” says Singer, who worked at the site with U.S. Geological Survey expert Wes Hildreth, who started the first systematic mapping of the area in the 1980s. “We hypothesize that this is what is inflating the crust,” Singer says. “It’s like a balloon blowing up the surface.”

History, says Singer, is usually a good guide to the future. Laguna del Maule has “had at least three million years of pretty constant igneous [molten-rock] activity, and about every half million years it looks like a fairly substantial, caldera-forming eruption. Are we overdue for another?”

A caldera is a ring-shaped structure formed when by collapse when a giant pool of magma is vented to the surface.

The questions we ask

“Volcano” and “prediction” are not words that geologists like to join together, but the essential goal at Laguna del Maule is to understand the situation well enough to answer a simple question: How likely is an eruption that would be large enough to affect the region or the planet?

How much do we need to worry?

Singer hopes that the 2013 exploration of Laguna del Maule will soon be augmented with a wider variety of analytic techniques:

These techniques gain precision if their data are merged, Singer says. Many methods “can give a fuzzy picture of what’s down there, but the more techniques you can bring to bear, the more you can tighten up the boundaries between different materials” and so get a better picture of the magma and its potential routes to the surface.

Need a date?

If you need a date, Singer is a good guy to know, at least if you want to date rocks. A specialist in geochronology, Singer uses sensitive instruments to squeeze out a date of formation for igneous rock, meaning when the rock solidified from cooling magma.

The overall goal at Maule is to tease out the timing of the many lava flows in the basin.

One dating technique relies on the radioactive decay of potassium into the gas argon, which follows a schedule set by the half-life of the isotope potassium-40.

Magma is hot, and any argon present will diffuse into the crust, but argon is trapped after magma cools into lava at earth’s surface. “Once it cools past a certain point, then argon stops diffusing, allowing argon produced from radioactive decay to build up,” says Nathan Andersen, a Ph.D. student in geoscience at Wisconsin who is dating recent lava flows at Maule.

Potassium-40 decays into argon-40, and so counting each isotope becomes the foundation for calculating the date of cooling.

However, potassium decays slowly, and this system has yet to date recent flows at Laguna del Maule, which are apparently younger than 2,000 years.

The eyeball on the highball

High-tech is eye-catching, but once you know what you are looking for, eyesight offers insight. Look at the large granite intrusions underneath Tatara San Pedro, a nearby volcano. The granite is apparently the remains of a magma chamber which cooled about 6 million years ago.

“It looks like a frozen magma body that is analogous to the magma body we think is active beneath Laguna del Maule today,” Singer says. Similar bodies of frozen magma have risen over 80 million years in California’s Sierra Nevadas. “But here, it’s now 2,500 meters above sea level. That’s 7,500 meters of uplift in 6 million years!”

The express elevator that is raising Laguna del Maule can be seen with the naked eye. White streaks on certain parts of the shoreline contain diatoms and ash that were deposited in the lake. “These are a sign that the uplift has been going on for many centuries,” Singer says.

The lake bench, 200 meters above the existing lake, shows an old shoreline that, when formed, was as horizontal as the lake itself. Singer suspects that the profile of the bench carries a long-term record of uplift.

Faults, which show how adjacent sections of rock have moved against each other, are another eye-catcher. Last year, the Wisconsin scientists found new evidence of horizontal spreading and faults; these structures show earth movement, and could facilitate the rise of magma and an eruption.

Thou shalt know thy rocks

If you know what you are looking at, small outcrops can play a large role in understanding the geologic history at Laguna del Maule. Analysis of the chemistry, minerals and texture of rocks can show that remote outcrops are remnants from a single eruption, or a single magma body. “When you start to see rhyolite on one side of the lake,” Singer adds, “and identical rhyolite on the other side, and you try to imagine how big the system must have been to produce both of those eruptions, that really grabs your attention.”

(Rhyolite, an uncommon type of magma that is rich in water and silica, and resistant to flow, is the most explosive and dangerous magma on the planet.)

Finding chemically similar lava over such a large area indicates that a large eruption is possible in the future.

Measuring the ground shaking

When the earth moves, the resulting vibrations convey clues about the planet’s internal structure. Both earthquakes and deliberate explosions can produce a “CAT scan of the crust,” based on how waves are transmitted, reflected, absorbed or converted into different waves, says Clifford Thurber, a seismologist at UW-Madison.

In the first months of this year, seismographs at Laguna del Maule were “detecting repeated swarms of earthquakes, clusters that happen close together in time and space,” Thurber says. “Those are hallmarks of magmatically active volcanic systems, but they do not prove anything. On the other hand, if it were seismically silent, one would have to wonder if anything is going on.”

After a swarm of earthquakes in March, 2013, scientists at the Chile’s Southern Andes volcano observatory issued a yellow alert, indicating that an eruption was possible in weeks or months.

Stronger and longer earthquake swarms and tremors are danger signs, Thurber says. “If we get sustained tremor, a low-level shaking that continues for hours to days, then we would get nervous. If we start to get very large earthquakes, 6 magnitude, it’s time to go.”

Thurber is introducing state-of-the-art computer analysis of seismic waves that will pinpoint arrival times more precisely. With improved earthquake locations, “We can do a better job of clarifying the structures that produce the earthquake,” Thurber says.

With a seismic expert on the line, we had to ask why the giant 2010 Maule earthquake did not trigger an eruption at nearby Laguna del Maule, just a few hundred kilometers the east of the epicenter. “It’s odd,” says Thurber. “This happens around the world. Sometimes a large earthquake triggers activity, and sometimes it does not. The volcano has to be ready.”

Gas attack!

Volcanoes can release staggering amounts of gas: Mt. Pinatubo coughed up an estimated 20 million tons of sulfur dioxide.

Carbon dioxide, a hallmark of basalt, is the big concern at Laguna del Maule, and
despite difficulties with two brand-new carbon dioxide meters, Glyn Williams-Jones, a volcanologist at Simon Fraser University in British Columbia, did find some elevated levels along the lakeshore in 2013.

“That means there is basalt entering the magma chamber from below,” says Williams-Jones.

Newly arrived, extremely hot basalt could interact with the existing rhyolite magma and boost the odds of eruption.

The Why Files

Helene Le Mevel, a graduate student, adjusts a meter that measures the local gravity field with astonishing precision. If significant amounts of magma are rising underground, gravity should be weaker in next year’s measurements — if the measurements are precise and accounts for the ongoing uplift of the area.

Electrical currents

To get a better sense of what’s happening under ground, geophysicists can measure electrical currents and magnetic fields inside Earth. “The surface is bathed by electromagnetic radiation from the sun, and there is an electrical response at depth,” says Singer.

The technique, called magnetotellurics, is used in geothermal energy exploration, and an energy company has already used it to find a shallow steam field just west of the caldera that could power a geothermal electric generator.

Magnetotellurics has already revealed that the crust around Laguna del Maule is about 40 kilometers thick, and that the magma body is about 5 kilometers below ground, Singer says. In the future, the technique could help define the size and location of melted crust near the magma chamber.

Gravely measuring gravity

Accurate measurements of gravity are another telltale about changes in the hot, molten magma. Because matter expands as it warms, magma is 10 percent less dense than surrounding rock, explains Basil Tikoff, a UW-Madison specialist in large-scale structure of the Earth, such as faults, old mountain belts and tectonic plates.

Gravity “does not have the resolution of other techniques, and it requires an enormous amount of fieldwork,” Tikoff says. “It’s a kind of geophysics that very few geophysicists do now.”

In March, Tikoff, graduate student Helene Le Mevel, and Williams-Jones installed 38 gravity stations on two lines crossing the center of uplift. The gravimeters are built around an ultra-precise spring that allows a suspended weight to respond to gravity. Although the meters are more than one-h century old, they are accurate to one part in 100 million. “If there is an earthquake, we have to turn the gravimeter off and wait,” says Tikoff. “If the land is going up and down, the gravimeter can see that, even if we can’t feel it.”

The pull of gravity decreases as  the instrument gets farther from the center of the Earth. “This instrument is so sensitive that if we went up a few stairs, you could tell,” Tikoff says. Therefore, Laguna del Maule’s pervasive uplift must be mathematically removed from subsequent measurements.

Baseline measurements taken in March and April will serve as reference points for subsequent surveys early in 2014. Located at the crest of the Andes, Laguna del Maule will be impassable until then due to its astonishing snowfall.

What comes next?

Laguna del Maule is a contradiction. To people who would be affected by a large eruption (which could include all of humanity in a super-eruption) it’s a threat.

But to geologists, it’s an opportunity to see how Earth is changing, and that is what draws Singer back. “The processes of deep Earth history are abstract,” Singer says. “I am more attracted to things that happen to the planet on a rapid time scale, such as glaciers and volcanoes. These take place on a human time scale.”

March, 2013, The Why Files

Gravimeters must be protected from vibration due to wind. Graduate student Tor Stetson-Lee blocks wind as Basil Tikoff measures gravity on the east shore of Laguna del Maule. That flying-saucer-on-a-stick is a GPS receiver able to measure altitude in millimeters.

The explanation for the new activity is pretty clear, Singer says. “There is no reason other than new magma to explain uplift of that size.”

The rapid uplift, combined with swarms of small earthquakes, apparent releases of carbon dioxide, and spreading of faults cannot go on forever. If they continue, the magma’s upward pressure will eventually exceed Earth’s ability to contain it.

Then Laguna del Maule erupts.

Until then, geoscientists see a chance to observe in real-time processes whose results can be seen all over the planet, and there is lots to be learned before the eruption, says Singer, who normally looks, forensic-style, after the eruption. “I try to reconstruct the history of magmas that feed the volcano, and how the processes inside the magma affect the way the volcano erupts, whether it’s explosive or passive. I try to stay away from them when they are erupting.”

Volcanoes usually emit a sequence of warnings, including a critical change in seismic signals, but nobody knows if Laguna del Maule will break the mold or follow it, adds Thurber, the seismologist. “We don’t have perspective. Studies that have been done on systems like this have exclusively been done after they have blown their top.”

Volcanoes are inherently unpredictable, especially the bizarre giants like Laguna del Maule, Thurber says. “We have no idea what the timeframe is to go from the rapid inflation we see now to an eruption. It could stop inflating and say ‘I’m done for now.’ It’s completely unpredictable; it could erupt tomorrow, next week, next year, next decade, next century. We don’t know for sure it is going to blow, but it sure as heck looks like it. If it erupts, the fact that a study had been done beforehand would be phenomenal, and unique in the world.”

A field experiment in South Africa finds that vervet monkeys change their taste in food when they join a new group, providing further evidence for “social learning” in animals. When the experiment started, monkeys were fed blue or pink corn. One color had the usual taste, but the other was politely described as “highly distasteful.”

That quickly taught the monkeys a lesson on palatability.

The researchers came back four months later to observe what newborns were eating. No shocker: they followed mom’s advice regarding corn color, even though both colors now tasted the same.

Then came the interesting part. As vervet guys mature, they migrate and join new groups. Intriguingly, 10 of the 15 migrant males immediately changed their preference to match the culture of the new group; four others had to wait to switch until the dominant males had eaten their fill.

“We designed the study for infants, which is why we had the four-month gap, so the babies would be ready for solid foods,” says first author Erica van de Waal, a post-doctoral researcher at St. Andrews University in Scotland. “But when we followed the male migrations, Wow! This monkey was trained to eat pink corn, and… to see him join the new group who all eat blue, and he decides, ‘No, I have to eat blue.’”

(Tactical note: The researchers tested both combinations. For half the groups, pink started out as yucky, for the other half, blue started out tough on the tongue.)

Mother knows best

Following the local lead has obvious evolutionary benefits, says van de Waal. “In a foraging diet, it’s really important” to benefit from the local knowledge.

Because females stay home on the range, they have enough local knowledge to survive. Not so for the moving man, van de Waal says. “He may see a new species of tree, or the toxic composition of edible fruits will change. They need the best local information to survive in the new environment.”

That’s especially true because males make multiple migrations, and thus seldom become experts in the local restaurant scene. “You could think that a dominant male that was in a group for 10 years would have as much knowledge as the females, but these males change groups a lot,” van de Waal says.

Although both colors had the same taste in the new location, even after migrant males tasted their previous preference, van de Waal says, “They still thought, ‘If the locals want that one, it must be better.’

“We know that vervet monkeys are opportunistic and adaptable, they have spread across Africa, so as soon as they found that both foods taste the same, we thought the ratio would drop to 50-50,” van de Waal says. “Not at all. Even the ones with previous knowledge adopted the new normal color.”

Shocker: This guy didn’t want advice

What about that 15th male, who remained his allegiance to the corn color of his youth? “It’s kind of strange,” says van de Waal. “He entered a group where the dominant male had disappeared, he was a big, strong adult male, a full adult, and he directly became the dominant male, and did not seem to care about what the others were eating.”

And that suggests that the survival advantages of changing food preferences to suit the “culture” in a new location may not fully explain the results, van de Waal says. “Maybe it confirms there is something social going on.”

At any rate, you can’t fool the true experts, she says. “The females did not try the color he was eating. The dominant females are always conservative; he did not influence the dynamic of the group.”

On the other hand, “This is sample of one,” says van de Waal. “Maybe he is just a stupid male that does not care what the others are doing.”

It’s been 15 years since a University of Wisconsin-Madison researcher isolated embryonic stem cells — the do-anything cells that appear in early development. It’s been six years since adult human cells were transformed into the related induced pluripotent stem cells.

And yet the early hope to grow “spare parts” — turning stem cells into specialized cells for repairing a failing brain, pancreas or heart, remains mostly promise rather than reality.

Researchers have since found how to transform stem cells into a wide variety of body cells, including heart muscle cells, or cardiomyocytes. But the holy Grail — tissue supplementation or replacement — remains tantalizingly out of reach.

Last week, Why Files attended a symposium on treating cardiovascular disease with stem cells, at the BioPharmaceutical Technology Center Institute near Madison, Wis. We found the picture unexpectedly complicated: as multiple kinds of stem cells are grown and delivered in a bewildering variety of ways to treat a catalog of conditions.

So far, stem cells have not been approved to treat any heart disease in the United States.

Still, the need remains clear. Disorders of the heart and blood vessels, which deliver oxygen and nutrients to the body, continue to kill. “Today, one of every 2.6 Americans will die of some cause related to their heart,” writes Columbia University Medical Center.

Not an easy project

Heart muscle dies when a blood clot blocks the blood supply. Heart muscle does not regenerate, and a major attack can cause death or a lifetime of heart disease.

So why have injections of heart muscle cells grown from stem cells produced only transitory benefits? “There is a battle between the heart and what it is willing to receive,” says Warren Sherman, director of cardiac cell therapy at Columbia University Medical Center.

“Even with normal heart architecture, it’s not a very friendly place for cells to find a home,” Sherman says. “The fluid flow rate is so high that many things get pushed out.” And in the areas that are scarred by heart attack, “there is nothing for the cells to adhere to.”

As a result, “Cell retention rates are just horrible,” Sherman says. “You are lucky, with any [heart] disease, with any delivery method, if you have 5 percent of the cells present 24 hours later.”

The brain or pancreas, two other potential sites of cell therapy, do not suffer from these hindrances.

Researchers have injected muscle cells into blood vessels, inside or outside the heart. They have also injected cells into the muscle of a heart that is still beating. A batch of stem cells can also be seeded onto a “patch,” a fibrous glob that gloms onto the damaged muscle.

Got the money?

The large, phase III clinical trials needed for FDA approval of a biological treatment typically enroll hundreds of patients at multiple sites, which can be hideously expensive. “Any phase III trial is going to cost at least $100 million, and it goes up from there,” says Hunt.

Even when preliminary results are promising, trials can be torpedoed when the sponsoring company changes its business goals, is bought out, or runs short of money.

For example, the “MARVEL” study, which grew stem cells from the patient’s muscle into early-stage heart muscle cells, or myoblasts, produced “a strong indication of improvement in symptoms and exercise capacity in 21 patients,” says Sherman, who played a role in the trial. “It was safe, but the company [Bioheart, Inc.] was broke … and that’s how it ended. Whether the results were positive or negative, we would have put up a number, and that number still does not exist.”

Stem cell trials must also account for procedures in particular medical fields, said Ann Remmers of Aastrom Biosciences. After a recent stem-cell trial for chronic limb ischemia, which reduces blood flow and can require amputation, “we needed to think through the practice patterns of vascular surgeons. We wanted to treat subjects who had no further options for surgery, but the surgeons we work with are very talented,” and were able to do reparative surgery until shortly before amputation was needed. “The vascular surgeons are making the decisions based on what is best for the patient, and we needed to have thought more about how to integrate the trial into their practice,” Remmers said.

Special stem cell delivery

To date, stem cells have not done much to help people with heart disease. Despite some limited improvement, by six months, the benefits have generally washed out.

“Typically you just give a single dose,” says Eric Schmuck, who works with Amish Raval, an assistant professor of cardiovascular medicine at UW-Madison. “Nobody has done two doses.”

And so Raval and Schmuck are testing a two-dose “prime and boost” strategy. The mesenchymal stem cells they are using originate in the placenta, and are known to fight inflammation, slow down the immune system, and promote blood-vessel growth.

In an ongoing test with pigs, the prime dose is given intravenously shortly after blood flow to part of the heart is stopped, Schmuck says. The resulting inflammation seems to attract the stem cells, which calm the inflammation.

Thirteen days later, 13 injections of the booster dose — totaling about 100 million cells — are squirted into the edge of the damage. “The first dose alters conditions to make the heart more receptive to the second dose,” Schmuck says. “When you reduce inflammation and stimulate blood-vessel growth, the cells have an easier time grafting.”

The experiment is ongoing, but there are early measurements in blood pressure and volume, and heart size and weight, Schmuck says. The treated hearts show a more regular heartbeat, without a systemic immune response.

Curiously, Schmuck doubts that the benefits come from cell replacement. “I think the cells secrete good vibes, juices, that either attract innate stem cells from the heart or help preserve heart muscle cells that are damaged.”

If the study continues to be safe and beneficial, the researchers hope to propose a small human trial of prime and boost within a couple of years.

Meeting your matrix

In the body, most cells grow in a mushy, 3-D world, but in the lab, they grow on hard, flat dishes. This discrepancy may account for some of the difference between real life and lab-life results, says Brenda Ogle, an associate professor of biomedical engineering at the University of Wisconsin-Madison.

Ogle is exploring structures to hold stem cells in a more lifelike configuration, and she finds that mesenchymal stem cells differentiate much as they do on a 2D dish, when held in a lab-built 3D structure of polyethylene glycol.

However, the timing of differentiation is different, Ogle says, possibly due to altered activation of cell-surface receptors, or to the fact that “tissue culture takes place on a stiff, rigid surface,” while the 3D structure is more flexible.

The 3D structure that Ogle is testing contains bits of extra-cellular matrix (ECM) proteins, such as collagen, which normally separates cells. “People used to think of ECM as girders and beams, a structural support for cells,” says Ogle. “We now know that it has other important functions,” such as storing growth factors. “If there is tissue trauma and the ECM breaks down, that may release growth factors that help the tissue respond to damage.”

Ogle’s goal is to build a patch that could stick to the heart and deliver stem cells. Although a disturbing number of cells are flushed away with existing delivery technologies, Ogle’s lab has achieved 70 percent retention by delivering mesenchymal stem cells on a patch made of cow collagen.

Endothelial cells to the rescue?

On the inside, of blood vessels are lined with endothelial cells that help regulate blood pressure, prevent clots, and regulate transport of molecules in and out of blood. Endothelial problems are a cause and symptom of a variety of conditions, including stroke, diabetes and coronary artery disease.

Could endothelial cells play a role in organ regeneration? Yes, says Shahin Rafii, a Howard Hughes Medical Institute investigator at Weill Cornell Medical College. “People think of endothelial cells as inert conduits to deliver oxygen and nutrients. We think maybe they can be the magic bullet, that we can transplant them to promote organ regeneration.”

Like the prime and boost example, the effect is less likely to be cell replacement and more creating a hospitable niche for existing heart cells.

The cells that line capillaries are in a unique position to affect stem cells, Rafii says. “Every stem cell, everywhere, resides next to a capillary. If I tweet a molecule through the capillaries, within seconds, every stem cell in body will know what is going on.”

Rafii adds that endothelial cells trigger growth in organs that are able to regenerate, like the liver and bone marrow. But the regrowth fails if, for example, the endothelial cells come from a different tissue.
Focusing on regeneration is an alternative path to stem-cell therapy, Rafii says. “I argue that if we can engineer organ-specific endothelial cells and transplant them, they will find the right zip code [in the target organ], and cause regeneration.”

If the endothelial cell hypothesis is unusual, so is the proposed source: cells gathered from amniotic fluid during amniocentesis, a common test for fetal health and gender.

“I believe amniotic cells can be used to regenerate bone marrow, lung and liver, if we can solve the immunology problem,” Rafii says. Discarded tissue from the 1 million amniocentesis procedures performed each year in the United States could provide an enormous, diverse stockpile of cells for transformation and transplant.

If Rafii is correct, understanding the signals from endothelial cells could be a significant advance, Kamp says. “Maybe the endothelial cells are telling the heart stem cells and other repair mechanisms to turn on. If you have sick endothelial cells, like with coronary artery disease, those endothelial cells are probably not singing the right song. If we could help them, we could help the heart.”

Making sense

Nobody can say where, how and when stem cells will become an accepted treatment for cardiovascular disease. But if you combine the extraordinary promise of these cells with the scientific creativity and the profit potential of any treatment that really restores heart muscle, it’s almost inevitable that hearts and blood vessels will eventually benefit from stem cell therapy.

Kamp thinks considerable progress has taken place: “Cell therapies are advancing. We are testing different cell products in patients with heart disease. The real question is what is going to be the right cell for the right job. There are different diseases with different needs, and different cell products and delivery mechanisms. All that has to be worked out, optimized and tested. Clinical trials to develop these take time.”

Modified from original by American Heart Association

Rates of mortality are diminishing from stroke and coronary heart disease

But patients are still dying, and stem cells are only available from a few small clinical trials within the world regulated by the U.S. Food and Drug Administration. For patients, that’s frustrating, says Sherman, who has been involved with cardiac cell therapy for many years; “I feel greatly for patients out there. We have raised the level of expectation, from the moment stem cells hit the front page, and fairly so, for good reason. Yet it has dragged on, again for good reason, and we still don’t know how to advise them.”

Basic breakthroughs always seem to take too long, Kamp observes. Research into implantable defibrillators, used to stop heart attacks by stabilizing heart electrical rhythms, began in the 1960s, but they were not in wide use by surgeons until the ’90s. “It’s not unusual for these revolutionary technologies to take a decade or more before they start to enter clinical practice.”