Climate Scientists to Politicians: Enough Already

A pretty remarkable letter was published in the journal Science this week, signed by 250 members (including4 University of Chicago scientists) of the National Academy of Sciences and calling for “an end to McCarthy-like threats” surrounding climate change. The letter makes a stand for reason on both climate change specifically and science in general, arguing that the scientific process of constantly questioning and improving the knowledge of a particular subject should not be misinterpreted as flaws.

When someone says that society should wait until scientists are absolutely certain before taking any action, it is the same as saying society should never take action. For a problem as potentially catastrophic as climate change, taking no action poses a dangerous risk for our planet.

The letter comes on the heels of Oklahoma Sen. James Inhofe suggesting in March that U.S. and British scientists should be criminally investigated for their role in the “ClimateGate” hacked e-mails incident. Michael Mann, the Penn State climatologist who created the famous hockey stick graph showing the recent rise in global temperatures, was cleared by his university of any misconduct charges, but was targeted this week by Virginia Attorney General Ken Cuccinelli. Such efforts are political grandstanding at its most despicable, and seriously endanger the ability of scientists to conduct research in an open and unpolitical forum. Great coverage, as always, by Andrew Revkin at Dot Earth.

2010 BIO Coverage Roundup

To wrap up BIO week, I thought I’d cast a net for some of the other commentary from this week’s conference in Chicago. Bruce Japsen of the Chicago Tribune saw part of Al Gore’s speech and focused on how the global recession wounded the biotechnology industry. Tuesday’s keynote session with George W. Bush and Bill Clinton was controversially closed to the media, but Forbes ran a perspective on the event from a conference attendee. Industry magazine Fierce Biotech and the San Diego Biotechnology Network were also grinding out gavel-to-gavel coverage alongside our own.

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Three days and 7,500 words later, I’m happy to be back at my office desk this morning after an exciting week at the BIO conference. For those of you without the time to wade into the coverage, here are some concluding thoughts and a selection of links to the most memorable parts of the meeting. If you want the real-time rundown, click for the coverage from Monday, Tuesday, and Wednesday.

I’ve never been to a conference quite like BIO. The ivory tower of academia is fortified enough that your typical scientific conference operates somewhat insulated from real-world dollars and cents, other than the constant calls for funding and the lavish laboratory supply displays on the exhibit floor. But at BIO, the world’s largest biotechnology conference, the conversation starts with business. Pharmaceutical companies advertise their wares, startups network with venture capital companies, countries and states tout their locale as fertile for biotech business, and countless panels discuss the impact of the world economy on the industry. The marketplace focus creates a different vibe, to say the least - from presentations handicapped by non-disclosure agreements to a significantly fancier dress code to audience questions that sound more like a shareholder’s meeting than a research seminar.

Those are not necessarily negatives - I only mean to point out how it was all a bit foreign to a former academic scientist such as myself. If nothing else, the emphasis on the bottom line produced more focused research talks - the science, in most cases, was expected to provide a concrete solution, not incremental progress. Biotechnology is a field vaguely-defined enough that those solutions were broad and ambitious: medical treatments, devices, and tests dominated the discussion, but there was also talk of ending world hunger with bio-engineered agriculture, rolling back climate change with biofuels, and protecting the world from misuse of biotechnology with biosecurity biotechnology. If occasionally one felt like the speaker was selling their science rather than presenting it for discussion - well, yeah, they were.

But with all the discussion of promising technologies for the future, the main obstacle appeared to be fairly low-tech: human communication. Many sessions hoped that the bright side of the global recession would be more partnerships between academic research centers and private companies, with industry helping academic scientists bridge “the valley of death” in commercialization while academia fills the gap created by industry R&D cuts. But the language barrier between the two entities doesn’t seem to be weakening, as evidenced by any panel where representatives from industry and university sat side by side. Disconnected motivations (profit vs. tenure), approaches (basic science vs. applied science), and pacing (quarterly reports vs. multi-year grant cycles) all would seem to make the academia-industry bridge an especially difficult construction project.

The other communication breakdown oft lamented at the conference was between the industry and the public. Any time a field comes together, an us vs. them mentality quickly forms - the sense that nobody but us understands just how critically important neuroscience or dentistry or insurance actuary is to the world. But biotechnology has its own battles to fight, after journalists and politicians have targeted products such as corn ethanol fuel and genetically-modified crops for reasons both valid and uninformed. Michael Specter, staff writer for the New Yorker, rightly said that many attacks against biotechnology are borne of unsubstantiated fear caused by scientific illiteracy. But Specter also criticized pharmaceutical companies for shooting themselves in the foot by being cagey with the press, sitting in “defensive crouches” rather than emphasizing the good things they do. A relevant lesson for a conference where media were blocked off from keynote addresses by George W. Bush, Bill Clinton, and Al Gore, save for access during the first five minutes of the latter speech.

But criticisms aside, I had a great time covering the conference. The enthusiasm of the scientists - be they from industry or university - was infectious, and the motivations of all involved are pure despite the smell of profit. The full potential of science can’t be realized if it is kept within laboratory walls, and while the process of distributing science to the greater public can be messy, it is absolutely critical if we are to improve the world around us. Here’s a roundup of the favorite things I saw this week.

The Gee Whiz Sessions

Building New Tissue with Nanotech

Stem Cells from Skin Outpace Stem Cells From Embryos

Artificial Pancreas? There’s an App for That

University of Chicago at BIO

The Chicago Innovation Pipeline

Translational Research Forum: Forging Better Partnerships and Making Trials Faster

Why Better Diagnostics Need a Better Health Care System

The Business Side of BioTech

The United States’ Narrowing Biotechnology Lead (ft. CNN’s Fareed Zakaria)

Surviving the Recession (post by Karla Melendez)

Biotechnology Battlegrounds

Improving the Science of Regulation (ft. FDA Commissioner Margaret Hamburg)

The Arms Race of Biotechnology

The Ethics of Engineering Nature

This is the third day of our coverage of the 2010 BIO International Convention, a massive biotechnology conference being held this week at McCormick Place in Chicago. Come back all day for reports from panels, lectures, and the exhibit floor on how scientists, government leaders, and industry hope to use the combined forces of science and technology to tackle some of the world biggest problems. For the first two days of our coverage, click here and here.

6:00 PM - Biotechnological Patriotism and the Petabye Age

Walking through the elaborate castles erected by countries from Europe, Asia, and South America on the exhibit floor (pictured below), an American might develop some anxiety about their country’s status as undisputed champion of biotechnology. That’s partially an illusion - if all of the kiosks for individual American states and U.S.-based biotech companies were pooled into one giant USA! USA! booth, it would take up the majority of the exhibition. But paranoia that the rest of the world is hot on America’s trail was palpable through the conference, with rumblings of new biotech epicenters in China and India rippling through McCormick Place.

A panel organized by Scientific American this afternoon sought to set some of those fears at bay, and the message was delivered through a persuasive moderator: CNN’s Fareed Zakaria. With his keynote address, Zakaria talked about the economic landscape as the world recovers from a global financial crisis, but said that the real economic story of the last 50 years was not bubbles and recessions, but the broader participation in the world economy. No longer is all the exciting innovation and economic development happening in a few North Atlantic nations, Zakaria said; now even small countries have robust, independent economies and an impact on the global system.

The downside of that phenomenon, for Americans at least, is that we are no longer the one place where the world’s biggest achievements are located. The biggest mall in the world, Zakaria pointed out, is no longer Minneapolis’ Mall of America - it’s the South China Mall in Beijing. The richest man in the world lives in Mexico City. The world’s largest refinery is in India. But the United States can still lay claim to the most highly-respected universities in the world, and the “extraordinary quantity of high quality research” that goes along with that system.

Joined by a panel of biotechnology industry leaders, the reassurance continued. China and India - while several orders of magnitude larger in population than the United States - are too concerned with building infrastructure to pose a near-term threat to American biotech expertise. The American investment system, which rewards creativity and understands that many big ideas fail, remains a model for the world. And as long as United States universities are perceived as the world’s best, they will attract the best students from around the globe to our shores - even if, increasingly, those students return to their home countries to apply their education.

With all those warm feelings, it was a little disheartening to find what I thought would be one of the day’s most engaging research sessions - on applications of computational science to drug discovery - to be also the day’s most sparsely attended. Fascinating, exciting research was presented by scientists from the University of Illinois and Argonne National Laboratory on how the rapid growth of computing power capabilities has made new types of experiments possible.

Emad Tajkhorshid showed animations representing the dynamic wobble of protein interactions, drugs and targets undulating like ocean waves - suggesting that scientists will no longer be constrained by the necessary simplifications of benchtop science. Rick Stevens, from Argonne, talked about grabbing a small soil sample and sequencing every organism within, grabbing potentially thousands of complete genomes - many of them never before seen - at once. As one questioner said, we’ve brought everyone into the genomic age, but the next step will be the petabyte age, an age of previously unfathomable computation enabling the creation of new science. Unfortunately, this afternoon there were few there to witness the new age’s early steps.

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Implantable pacemakers and defibrillators have been a staple of cardiology for decades. Offering round-the-clock protection against heart attacks and other issues, it’s not hyperbole to say that the devices have been a lifesaver for hundreds of thousands of people. But the majority of these implantable devices are still placed predominantly in older patients with heart conditions, with the average age of recipients consistently in the high 60’s in clinical trials. Because of the finite lifetime of an internal cardoverter defibrillator (ICD) or pacemaker and the difficulties associated with removing or replacing those devices, many doctors prefer to avoid those options in younger patients.

“That’s crazy,” said Martin Burke, director of the heart rhythm center at the University of Chicago Medical Center. “You have more to gain from a defibrillator if it saves your life when you’re 50 rather than when you’re 80.”

But some of the concerns over implantable defibrillators are legit. Classic ICDs and pacemakers require the electrical leads that deliver the shock to be placed inside the heart, where any infection can be a serious complication. The sensory system that tells the defibrillator to fire sometimes overreacts to benign changes in heart rhythm, causing unnecessary shocks. Flexible materials must also be used due to the hostile environment inside the heart - “It’s a 98.6 degree, dynamic environment that pumps like a piston 60 to 100 times a minute; it’s a miracle they last 15-20 years in my mind,” said Burke, who is a specialist at removing ICDs as well as implanting them.

So Burke has been part of a lengthy effort to improve the technology of ICDs, with a new device - the subcutaneous-ICD, or S-ICD - that finally reached the clinical trial stage this year. Last month, Burke performed the first S-ICD implantation in the United States upon 38-year-old Brooke Bergeron, who suffered a heart attack last year while giving birth to her fourth child.

The subcutaneous ICD changes the location of the leads from inside the heart to just beneath the skin over the sternum. If an infection should occur in that location, it would be less dangerous, and removing the leads would be a less difficult process. While the added distance from the heart means a more powerful shock is delivered by the S-ICD (about 2.5 times stronger than traditional ICDs), the power is still well within a safe range, Burke said. And patients should experience fewer of those shocks, thanks to an improved monitor system that measures more complex heart rhythm characteristics to separate out dangerous cardiac events from false positives.

“We’ve been shocking people like this for 40 years, that’s no different. The big change is the position of the electrodes under the skin and the sensor,” Burke said. read more

Perhaps the most famous neuroprosthetic device in movie history shows up at the end of The Empire Strikes Back. In the final scene, Luke Skywalker  is fitted for a new, robotic hand to replace the one so cruelly lopped off by (spoiler alert!) his father’s lightsaber. To test out the new hand, Luke first flexes it a couple of times, then allows a droid to poke it in several places with a thin needle. That latter part is actually an important test, verifying the sensory ability of the prosthetic to mimic a real hand’s response to pain or pressure.

Last week, we wrote about BrainGate, a neuroprosthetic that allowed some quadriplegic subjects to control a robotic arm with their brain activity. But a successful prosthetic limb, whether for a quadriplegic or an amputee, would need to have not just motor control, but also some semblance of sensory feedback replicating the ability to touch and sense the limb’s position in space. Imagine if you could move your hand but couldn’t feel it - tasks such as picking up a coffee cup without looking, catching a ball tossed your way, or removing your hand from a hot stove would become considerably more difficult. So while some scientist focus on the commands that travel from brain to hand and direct movement, others study the messages from hand to brain that convey touch information.

That’s the research goal of Sliman Bensmaia, assistant professor of organismal biology and anatomy, who provided the excellent Star Wars example. Bensmaia, who joined the University of Chicago faculty last summer, studies the neural basis of perception, how the sensation of touch is represented in the brain. Some of his most interesting studies have found ways in which the somatosensory system (the neurobiological term for touch) resembles other sensory systems such as hearing and vision.

In a paper published last month in PLoS Biology, Bensmaia and colleagues identified in the somatosensory system a mechanism already famous in the visual system. Visual direction selectivity is a classic topic of neuroscience classes based upon experiments performed by David Hubel and Torsten Wiesel, part of work on the visual system that eventually won them the Nobel Prize for Physiology or Medicine in 1981. Recording from the visual cortex of cats as they were shown different stimuli, Hubel and Wiesel found certain neurons were only activated when the stimulus moved in a particular direction. So when a dot or a bar was moved from left to right, a particular neuron would rapidly fire. But move the same dot or bar right to left, and that same neuron would be silent.

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The first patient in the UCMC's 256-slice CT scanner, the mummy Meresamun

Radiation had a bad reputation to overcome. Known for a long time for killing its discoverer and by frightening yellow-and-black warnings, the view of radiation has softened over the years as scientists and physicians corralled its powers for good. Whether used for screening or diagnosis in the form of X-rays and CT scans or therapeutically to kill tumors, radiation has become an essential tool for physicians.

But even with all these beneficial uses, radiation remains dangerous. A recent New York Times article discussed cases where patients received overdoses of radiation during medical procedures, usually due to computer programming errors undetected by the technicians. On the heels of that report, the Food & Drug Administration - which has oversight over medical devices - unveiled a new initiative to reduce unnecessary radiation exposure. Officials hope to improve patient safety by establishing tighter requirements for manufacturers of medical imaging devices, revising the accreditation process for those who use such devices, and conducting more research to find what level of radiation exposure is safe and appropriate for patients.

I asked Michael Vannier, professor of radiology at the University of Chicago Medical Center, to explain what these changes meant for the field and patients. Vannier said that he and his colleagues welcomed the attention being paid to these issues, even as radiologists and manufacturers were already seeking new ways of getting the maximal benefits from a minimum of radiation. At the Medical Center, a state-of-the-art 256-slice CT scanner acquired in 2008 provides higher quality scans than previously possible using 30 percent less radiation, Vannier said - and a computer upgrade scheduled for next week will reduce that radiation by a further 40 percent.

“What will happen, I think, is that the manufacturers will add capabilities to the instruments that make it possible to much more automatically and reliably monitor and minimize the dose,” Vannier said. The rest of our conversation is available below.

Why is the FDA initiative happening now, and why is it necessary?

Vannier: Well, you have several incidents that have attained a lot of notoriety. But what’s also happened is that CT scanning has become extremely popular. Your chances of having a CT scan in your lifetime are extremely high, because it is a very versatile and highly available technique. But it does use X-rays, and the dose you receive from a CT scan is higher than the dose received from X-ray techniques as a general rule. You don’t want to do them unnecessarily.

The second thing is that the CT scanners themselves have improved in their dose efficiency very significantly over the years. If a scan is done with an older scanner, it may very well require a higher dose than the state-of-the-art equipment, which means that getting the same exam in different places can mean different doses received. Even if you know what kind of exam you’re getting, the instrument doing it doesn’t necessarily tell you that the dose is low.

The third thing is the general facts of physics that govern how CT scanners work. If you give a minimal dose you can get an acceptable level of noise in images and the quality can be very high. But if you double the dose, you may see no improvement in image quality, so it’s deceptive in that way, and there’s a potential of overdosing or selecting the wrong dose setting. It takes special care to ensure that the dose is maintaining the standards that are held to that we call ALARA - As Low As Reasonably Applicable, which is the FDA-mandated standard.

In the past, for CT scans in general, it was very difficult to look at scans and tell what dose was used. In the latest scanners, which we use for exams here today, it actually puts a record of the dose in with the images, a printed-out diary or record, if you will. It’s possible to know with a high degree of confidence exactly what dose was received, whereas in past years it wasn’t possible, and people using older equipment may not be included in such a system.

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News outlets reported this week on a new JAMA study showing that having a heart defibrillator implanted by an electrophysiologist produces fewer complications for patients than if a doctor outside that specialty does the procedure.

I asked Martin C. Burke, DO, to comment on the article and the background that makes this important for patients and physicians, and he graciously agreed. Here is Dr. Burke’s post:

The new JAMA article regarding physician certification for implantable cardioverter defibrillator (ICD) implantation and patient outcome is interesting to me as a practicing electrophysiologist, or electrician of the heart, as well as a trainer of the next generation of electrophysiologists.

In 2004, the medical society that represents the heart electricians called the Heart Rhythm Society or HRS published criteria for certification that allowed non-electrophysiologists to implant ICDs without going through the rigors of a fellowship in clinical cardiac electrophysiology.  The electrophysiology fellowship training pathway provides a one- or two-year intense exposure to the management of heart rhythm disorders as well as training in the complex interventional procedures such as the ICD implantations and more complex cardiac resynchronization ICD implantations mentioned in the JAMA article.  The HRS certification criteria for non electrophysiologists has been used by hospitals and third-party payors to allow non-electrophysiology board eligible or certified physicians to get credentialed by hospitals to implant and get paid for such implants.

At the time of the publication of the 2004 paper, the membership of  the heart rhythm society was mystified as to why our own society would sanction such a document and essentially ‘throw under the bus’ our training pathway in heart rhythm disorders that we take quite seriously.  We as the heart rhythm society and I as a trainer of electrophysiologists have spent the last 20 plus years advancing the science and application of such devices in a methodical and expert way.  So, the logical deduction is that this policy has been the agenda of the device manufacturing companies who felt that there weren’t enough cardiac electrophysiologists to meet the needs of the public indicated for such devices.  

This is an incendiary topic as the financial implications at stake are large for all parties. Consequently there has been great controversy within the HRS membership, and it has recently bubbled into a call for our medical societies to sever all relationship with industry, a typically American over-reaction. Industry working with clinician scientists is of huge value to society at large as long as it is disclosed and managed ethically.  Of more concern to me are cases where study authors do not disclose potential conflicts of interest - a practice that remains distressingly common.

Still, patients should be assured that in science, the true path eventually becomes evident and now patients can move forward with expert device implantation and management with the best-trained physicians in the world to do so: the clinical cardiac electrophysiologists.  

You’d rather not live without any organ, but some are easier than others to replace with technology. Kidney fails? Get dialysis. Diabetes saps your pancreas? Take insulin. Heart gives out suddenly? Try a left ventricular assist device.

Credit: HepaLife

But the liver poses a special problem. Its biochemistry is so complex that no one understands all the functions it serves, or the details of how it works. We do know it’s essential for blood clotting and for removing a wide range of toxins from the bloodstream. Acute liver failure can lead to death within 48 hours. Yet even the liver’s well-defined functions are difficult to mimic completely. Then there are the thousands of proteins the liver produces, many of which have poorly understood roles in the body.

All of that makes it hard for artificial livers to do much more than help patients survive a few more hours while they wait for a donor organ. Even the term “artificial liver” is a bit misleading, because most of the devices rely on liver cells of some kind. Duplicating their function from scratch is just too difficult. (Imagine if heart assist devices had to use actual heart muscle cells.)

As this Forbes piece observes, several companies have gone out of business trying to make artificial livers. One of the rare success stories that the story cites is a University of Chicago patient, Amy Petrovic, who nine years ago survived on a synthetic liver for a few days - long enough for her condition to improve so she could survive a liver transplant operation. 

Attempts to make reliable devices keep coming - one company this week announced plans for a new Phase III trial of an artificial liver system, and a separate trial started last month. But stories like Petrovic’s also underscore the immensity of this challenge, and the limits of medical knowledge. Many hurdles in medicine are purely technological in nature. In this case, researchers don’t know exactly where the technological intervention should start, because they don’t fully grasp the underlying biology.