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Monday, 11 May 2015

On this day in History - Robert Koffler Jarvik was born

Robert Jarvik, MD is widely known as the inventor of the first successful permanent artificial heart, the Jarvik 7. In 1982, the first implantation of the Jarvik 7 in patient Barney Clark caught the attention of media around the world. The extraordinary openness of this medical experiment, facilitated by the University of Utah, fueled heated public debate on all aspects of medical research. But as doctors learned how to achieve excellent clinical outcomes in subsequent patients with the Jarvik 7, the press and public largely lost interest in the subject. As a result, outdated and erroneous accounts have made their way into mainstream discussions of the Jarvik 7 time and time again. 


Robert Jarvik

 Artificial Hearts in Context

In essence, two types of artificial hearts exist: the total artificial heart — which is implanted after the natural heart is removed — and the ventricular assist device — which is implanted to assist the natural heart, leaving the patient's own heart in place and still functioning.

"Removing a person's heart is one of the most dramatic surgical procedures one can imagine," says Dr. Jarvik, who began developing a tiny ventricular assist device, the Jarvik 2000, in 1988. "It is no surprise that more public attention is given to replacing a heart than to assisting one. But consider this question: If you had a failing arm or leg, would you rather have the best-possible artificial limb or a device that allowed you to keep your own arm or leg?"

The question is rhetorical. But while ventricular assist devices find wider application in patients than total artificial hearts, experts view the two as complementary treatments. For example, a total artificial heart is required when an assist device will not do, as in cases of biventricular failure when both sides of the natural heart falter.

In the 60s and 70s, mechanical hearts were being developed by the National Institutes of Health (NIH) but were largely unknown to the public. Then in 1967, Christian Bernard performed the first human heart transplant, an event that generated worldwide interest: People were suddenly aware of heart replacement as a way to treat a failing heart. In 1969, Denton Cooley performed the first implantation of a temporary total artificial heart, and the primitive device sustained the patient for almost three days until a donor was found through an urgent appeal in the press. After another decade and a half of NIH-supported research, the Jarvik 7 heart became the first total artificial heart implanted as a permanent replacement for a hopelessly diseased natural heart.

The First Jarvik 7 Patients

At the University of Utah on December 2, 1982, William DeVries, MD implanted the Jarvik 7 total artificial into Barney Clark, a Seattle dentist who volunteered to undergo the pioneering procedure because he wanted to make a contribution to medical science. Dr. Jarvik recalls that, before the surgery, Dr. Clark told doctors that he didn't expect to live more than a few days with the experimental heart, but he hoped that what the doctors learned might help save the lives of others someday.

Dr. Jarvik, who headed the company that manufactured the Jarvik 7 heart, agreed with University administrators to give no information to the press directly: no press releases and no interviews. Information would flow through the University press office, instead. The stated goal was to adhere to the highest ethical principles and to conduct this important medical research openly, with no effort to influence or restrict the press. Little press was desired or expected. The University held a briefing before the historic surgery, and attendance was moderate.

"The news about Barney Clark stunned the doctors by making headlines around the world", Dr. Jarvik says. "Enormous public interest developed, and hundreds of reporters converged on Salt Lake City to cover the story, and the University began to give them daily briefings, which were completely uncensored. All medically significant events in the post-operative course were reported, successes and setbacks alike."

The briefings were educational and contained much medical information, including explanations of basic physiology, interpretations of laboratory tests and x-rays, and lengthy question-and-answer sessions. All of the complications were fully reported, as well as the effectiveness of the mechanical heart at maintaining Dr. Clark's normal blood flow and sustaining his life.

"The sheer volume of information and the extraordinary degree of transparency created a sort of medical experiment in a fishbowl," Dr. Jarvik says. The University of Utah achieved its research and educational goals, but the press coverage seemed to leave its readers with unreasonable hopes and expectations: Many began to believe that artificial hearts would soon be commonplace and all but solve the problem of heart disease. The intense attention also attracted critics who apparently knew nothing of Dr. Clark's generous intentions and labeled him a "human guinea pig." Later, Dr. Clark's widow attempted to change this misimpression in order to give her husband the humanitarian credit he deserved. But Mrs. Clark received much less press than the critical commentary, and her mission ultimately foundered. Before another case could be conducted, Dr. DeVries, the surgeon, accepted an offer to join the research program at Humana Hospital in Louisville, Kentucky, and took his expertise there.

The next several implantations of the Jarvik 7 heart, conducted by Humana — a national hospital chain — were handled like the first: with the release of extensive medical information and an open press policy. The second Jarvik 7 implant took place in 1985. Bill Schroeder, the patient, did so well initially that when President Ronald Reagan phoned him with get-well wishes a week later, he asked the president why his social security check was late. (It was hand-delivered the next day.) Mr. Schroeder gave optimistic interviews to reporters and even joked that his noisy drive console "sounded like an old fashioned thrashing machine." But only two weeks after surgery, he suffered a serious stroke that left him unable to speak. Mr. Schroeder later moved from the hospital and lived with his wife in a nearby apartment, which had been outfitted with the special equipment he needed, including an air compressor and emergency generator. When traveling, he used a portable, compressed-air power system, which weighed about fifteen pounds. During his time on the Jarvik 7, he visited his hometown in Indiana and rode down Main Street in a parade, attended a basketball game, and went fishing, but in a limited way: He had many medical problems, including other serious strokes and infections. In all, Mr. Schroeder lived 620 days with his heart function restored but handicapped by his complications.

Three other patients received the Jarvik 7 heart for permanent use over the next year — two more in Louisville and one in Sweden. One patient died of bleeding a week following the operation; the others lived 10 months and 14 months. As it turned out, the Swedish patient was a man accused of tax evasion, but after his heart was removed, he was declared legally dead because under Swedish law, a person was dead when his or her heart stopped beating. The charges against him were officially dropped. The day he received the news, the patient was elated: He joked to his doctors that the old saying about nothing being certain but death and taxes isn't true.

The Jarvik 7 Today

After the first five permanent cases, the Jarvik 7 heart became more widely used as a temporary total artificial heart, bridging patients to transplant. The sixth patient lived five years after a donor heart was found, and the seventh patient lived eleven years with his donated heart. Another patient was bridged from the Jarvik 7 heart to a human heart that gave him fourteen more years of normal life. The press was unaware of these successes, or perhaps considered the subject old news, which, Dr. Jarvik says, was "more than fine" with the doctors involved. But as time went on, the press began reporting erroneously that use of the Jarvik 7 heart had halted after the first five. Later this turned into reporting erroneously that the Food and Drug Administration (FDA) had banned its use. Still later, this turned into reporting erroneously that the Jarvik 7 heart was a failed experiment: 

The press had begun to believe its own errors.

Since 1982, more than 350 patients have used the Jarvik 7 heart, and it remains in use today. The first few patients lived an average of 10 months (when their life expectancy was only days to weeks). Complication rates were high. "That's where the press stopped doing research and checking facts and instead began to publish mistake after mistake after mistake," Dr. Jarvik notes. All aspects of the experience, from the role of public funding of the research, to the ethics of human experimentation, were debated, but often on a foundation of misinformation. Newspaper and magazine articles with outdated and mistaken accounts appeared. Books with numerous errors were published. In the meantime, doctors gained experience with the Jarvik 7 and learned how to manage their patients more effectively and with fewer complications.

"Knowledgeable doctors watched with amazement as glaring errors appeared in print and then were repeated again and again as newspapers and magazines copied earlier stories and each other and didn't take the time to get information from original sources," says Dr. Jarvik. "Very rarely did I receive a phone call to check the facts. For example, the press wrote repeatedly that Dr. Clark died of a stroke. In fact, he never had a stroke at all. The press wrote over and over that the console a patient needed to power the heart was 'as large as a refrigerator.' In fact, the home console is about half that size, but more significantly — the portable power system was only the size of a briefcase."

And there's more, says Dr. Jarvik. "The press also wrote that the Jarvik 7 heart caused a high rate of strokes and infections. The press didn't notice that as more cases were done, these rates plummeted, yet the device was the same. So the device alone was never responsible for the earlier complications. Rather, doctors needed to learn how to manage their patients more effectively: That is the point of such research in the first place."

Perhaps the most glaring error of all is one that pops up from time to time in the diatribes of some self-proclaimed pundits: that the Jarvik 7 heart was a failed experiment. In fact, it has achieved the highest success rate of any type of artificial heart or assist device that has ever been developed.  Today, the Jarvik 7 heart is available at about ten medical centers in the United States, Canada, France, and Germany under the name CardioWest total artificial heart. (Ownership has changed hands several times, but the device 
design remains essentially unchanged.)


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Tuesday, 5 May 2015

When will we find aliens?

For the first time in human history, we have the means to answer the question.

Chris McKay's quest for extraterrestrial life started in 1976, when Viking 1 and 2 landed on Mars. Touching down on Mars for the first time was a big deal, sure, but the then-first-year graduate student was especially excited because the landers found what appeared to be signs of Martian life.

The spacecraft found that something in the dirt - possibly microbes - was taking in nutrients and producing gases like carbon dioxide. But when instruments failed to find any organic molecules, which are the building blocks of any organism, scientists concluded that no, aliens weren't living in the dirt.

To this day, however, scientists like McKay are still baffled by the Viking data, which never conclusively supported the existence of life, but were tantalizing nevertheless. For McKay, now a planetary scientist at NASA Ames Research Center, those results launched a career in astrobiology, despite the warnings of other scientists at the time. "Not only did they tell me not to," he says, "they made fun of me for being interested in it."

Four decades later, he's enjoyed some vindication. As robotic space probes continue to explore the solar system, visiting planets, moons, and asteroids, they're finding watery environments where microbial life could grab hold. Science can actually apply itself to the question instead of it being purely philosophical.

Outside the solar system, astronomers have discovered thousands of worlds - and they estimate our galaxy alone could be filled with hundreds of billions of planets. Many could be similar to Earth, with oceans, an atmosphere, and, yes, life.

In the coming decades, new space probes and telescopes will search for signs of life in the solar system and beyond. "We have a decent chance for finding Earth-like planets and evidence for life by sometime in the early 2030s," says Jim Kasting, a planetary scientist at Penn State University in the US.
Telescopes are used to eavesdrop on distant civilisations

And for the first time in human history, scientists have a plan and the means to answer the question of whether we're alone. "The fact that science can actually apply itself to the question instead of it being purely philosophical is very exciting," says Jason Wright, an astronomer also at Penn State. "It might be a long shot that we can do this, but the question is so compelling."

Undoubtedly, the most exciting kind of alien life would be the intelligent kind: the ETs or the ones depicted in Carl Sagan's novel Contact. Despite Roswell and Area 51, such close encounters have yet to happen. But scientists have been searching for decades, trying to eavesdrop on radio signals from a distant civilisation. Today, for example, the SETI Institute listens with the Allen Telescope Array in California.

Most recently, Wright led a hunt for super-advanced civilisations that have colonised an entire galaxy. In the 1960s, the physicist Freeman Dyson suggested that aliens could power their civilisation using energy from their planet's star. Consuming that energy - to run computers, spaceships, or whatever aliens might need - will radiate heat, like how your laptop gets warm. If such a civilisation took over a galaxy, then you could recognise it by searching for galaxies that radiate more heat than expected.

After scouring through images of 100,000 galaxies taken with the WISE satellite, Wright's team came up with nothing. But that's just for the extreme case of a super-advanced, galaxy-conquering alien. Maybe aliens stayed local. To find out, he says, the next step would be to study the galaxies in more detail, to see if certain regions within each galaxy are producing extra heat. "That would be very unusual," he says. "I don't know how we would go about getting a natural explanation for that."

Still, the search for intelligent life remains a reach. After all, life has flourished on Earth for about 3.5 billion years, and intelligent life (if we consider humans to be intelligent) has been around only for the last 200,000. For most of Earth's history, life consisted of primitive microbes. If we're ever to find life elsewhere, it will probably be microbial. Some could even be in our own cosmic backyard.

One intriguing place to look for life is on Titan, Saturn's largest moon. It's got a thick atmosphere and is the only other place in the solar system covered in seas and lakes - only they're filled with liquid methane, not water. Scientists think liquid is important for life, but the fact that it's methane means any Titanian critters would be fundamentally different from any Earthling.

That doesn't make life impossible, just maybe less probable. Life on Titan would also have to survive frigid temperatures of about -180 degrees C.

For life as we know it, the most important ingredient is still liquid water. And spacecraft are discovering the solar system to be quite wet. In March, observations with the Hubble Space Telescope suggested that an ocean lurks beneath the surface of Jupiter's largest moon, Ganymede. Right now, the Dawn spacecraft is orbiting Ceres, a dwarf planet in the asteroid belt that's 40 percent water by volume, including a possible subsurface ocean.

Among the most promising abodes for life are Mars, Saturn's moon Enceladus, and Jupiter's moon Europa. On Mars, the best chance for life might have been in the past, when the planet was warm and filled with rivers and lakes. Today, Mars is barren and likely inhospitable.

Microbes might, however, be able to eke out an existence below the surface. "I'd say it's 50/50 as to whether there's life on Mars right now," Kasting says. If there is, though, he says it's probably buried as deep as a kilometre underground, where temperatures are warm enough for water to be liquid. Getting there and finding proof, however, might require astronauts drilling on Mars.

Detecting life on Europa might also require drilling. A thick layer of ice maybe several kilometres deep encloses a potentially habitable ocean. Scientists have wanted to go to Europa for years, and they may soon get their chance. The White House's requested budget for 2016 includes $30 million for such a mission. But landing and drilling is difficult and expensive, so if the mission comes to fruition, it will probably study the world from space.

Which is why McKay thinks Enceladus - which also might have a subsurface ocean - is a better bet. "As people realise how difficult Europa is and how inaccessible its ocean is, they're going to be naturally attracted to Enceladus," says McKay, who was part of a team that recently proposed a NASA mission to Enceladus.

The icy moon became a top destination in 2009 when the Cassini spacecraft discovered plumes of water shooting hundreds of kilometres into space. Those plumes, spraying straight from the ocean below, could contain telltale signs of life. "You fly through the plumes from Enceladus," McKay says. "That gives you the best chance of detecting life." No drilling required.

Such an alien-hunting spacecraft would look for two types of molecules: lipids and amino acids. Lipids include fats and oils, and are important for the structure and function of cells. Amino acids are the building blocks of proteins.

The thing about an amino acid is that it can come in two versions that are mirror opposites of each other, like a left and right hand. Of the 20 amino acids that make up life on Earth, 19 are left-handed. Maybe, the thinking goes, amino acids that are biological in origin must generally have the same handedness. Discovering such molecules would certainly suggest life. "That's a grand slam," McKay says.

Still, he admits, that's a fantasy scenario. Microbes might not reveal themselves so easily, or they might not be there at all. Space missions take time and money, so if one spacecraft doesn't find anything, you'd have to wait years for another shot.

Chances might be better outside our solar system, among the billions of other planets in the galaxy. While a mission within the solar system can visit only one place at a time, a space telescope can easily go through dozens or even hundreds of potentially habitable worlds. Instead of lipids and amino acids, such telescopes will look for other molecules: oxygen and other gases that reveal living, breathing aliens.

Building off the resounding success of the Kepler space telescope, which has found thousands of planets, NASA will launch its Transiting Exoplanet Survey Satellite, or TESS, in 2017. Like Kepler, TESS will search for planets that pass in front of their stars, causing a slight dip in starlight. But unlike Kepler, TESS will target planets closer to Earth, and therefore easier to study and detect life.

What's got alien hunters excited is that TESS will find targets for the James Webb Telescope, which, after launching in 2018, will search those planets for atmospheric gases indicative of life.

The idea is this: As a planet passes in front of its star, some of the starlight will penetrate the planet's atmosphere, which appears as a thin outline surrounding the disk of the planet. Depending on its chemical composition, the atmosphere will absorb certain wavelengths of light. By measuring which wavelengths of light get through, astronomers can identify the gases in the atmosphere.

Astronomers have already studied planetary atmospheres with Hubble, showing their methods are sound. With the more powerful JWST, however, they can analyse atmospheres in greater detail.

One of the gases they hope to find is oxygen, which doesn't sit around very long before reacting with other compounds. So to maintain a lot of oxygen in its atmosphere, a planet would need something to replenish it - something living. On Earth, plants and bacteria do the job.

Compared to Mars or even Enceladus, this could be the most likely way scientists find life. "If I was betting today, I would bet on oxygen on an exoplanet," McKay says.

But oxygen is just one gas. Earthlings, for example, produce thousands (just think of all the smells that people, animals, and plants make). Only a handful of them are abundant enough to be detectable from space, however, so astronomers are figuring out which ones could be realistic indicators of life. Some proposed so far include methane and dimethyl sulfide, which phytoplankton produce on Earth.

Of course, finding life won't simply be a matter of detecting gases. Non-living things - such as thermal vents and volcanoes - can spew out many of the same compounds. To determine whether a particular gas is biological in origin, astronomers will have to study the chemistry and the specific properties of the planet.

Even then, short of a message from ET, astronomers may only be able to give the odds for extraterrestrial life. "We won't be sure there's life there, but we may be able to work through all the scenarios and assign a probability," says Sara Seager, an astronomer at MIT.

Another issue is that no one knows what alien life really looks like, so the proposed biosignatures so far are based on Earth's life. "You don't want to be too targeted and only look for stuff like Earth," Wright says. "But you also can't be so general that you have no idea what you're looking for."

To go beyond Earth-based life, Seager wants to identify any and all gases that could be stable and abundant in an atmosphere, regardless of whether anything on Earth makes them. To see if they're viable biosignatures, she will work backwards, reverse engineering biological processes that could produce those gases.

If JWST is to detect life, it will have to get lucky. The telescope was proposed years before astronomers knew the galaxy had billions of planets, so it wasn't designed for planet or alien hunting.

TESS will find thousands of plants, but only some will be good targets for JWST. A suitable planet can't be too small compared to its star. Otherwise, the glare of such a bright star swamps the image, and you can't see the subtle signal from the atmosphere. According to Seager, observing a planet next to its star is like picking out a firefly next to a searchlight from 1,500 kilometres away.

"It's not going to be easy," she says. "We're only going to have a handful of planets to search for signs of life on."

TESS and JWST will also be limited because they can only study planets that pass in front of their stars, which requires a perfect alignment. If JWST fails to find anything, astronomers will have to wait for a specially designed telescope that doesn't rely on transits.

Such a telescope will observe a planet directly, but for that to work, something will have to block the light from the planet's star. One idea called Starshade, which Seager has worked on, is a spacecraft that unfolds like a parasol to block starlight, allowing a separate space telescope to peer into the planet.

The telescope will be able to observe an Earth-sized planet orbiting a sun-like star, something TESS can't do because the brightness of a sun-like star will overwhelm the planet. With more potentially habitable planets - and including truly Earth-like planets - the chances for detecting life improve. "For a direct-imaging telescope, I'd say the odds are pretty good," Kasting says.

If anything, the sheer number and diversity of planets is reason for optimism in the quest for extraterrestrial life. "We know that atmospheres are out there, we've studied many of them, so the possibility is out there for the first time ever," Seager says. "It would be foolish not to take this opportunity."

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