Zoloft is a popular drug used for the treatment of depression symptoms.

Depression is hardly new. The Roman physician Galen, in the second century A.D., expounded on the prevailing medical view that four bodily fluids, or humors, existed within all people but that the unique variation of these humors within people resulted in individual differences among people in their behavior and temperament. An excess of black bile, for example, indicated a melancholic personality.

Fortunately, a lot of scientific progress has been made since then in understanding depression to be an organic, brain-based medical condition that afflicts millions. In fact, an individual has a ten to fifteen percent lifetime risk of developing a major depressive episode. But as Dr. Karl Deisseroth, a Stanford neuroscientist and psychiatrist, told me during our interview for “Illuminating Depression”, “Diagnosis is a big challenge because in psychiatry, we don’t have a lab test. There’s not a blood draw that you can do as you might to check how your liver is doing or how your thyroid function is doing.” So given that the diagnosis of depression is based on clinical observation (most often done by a primary care physician), one can’t help feel that hard, empirical understanding of depression is somewhat lacking, especially when compared to diseases of other organs like the heart and lungs where tests do exist to gauge the presence of pulmonary and cardiovascular diseases.

This was the most interesting observation for me when working on this story. Imagine a medical disease that afflicts eighteen million people in the U.S. (26 million if you include Bipolar Disorder), for which more than 160 million prescriptions were filled in 2008, that is one of the leading causes of disability in the U.S., but a disease for which no definitive medical model of pathology exists. Increasingly, doctors are prescribing antidepressants to treat not just depression but a host of other medical conditions, including chronic pain and insomnia, some of which can co-occur with depression. Sure, we’ve made strides since the time of Galen’s bodily humors and the Freudian view of misplaced hostility and mourning to explain depression, but in some respects, we’re still in the dark about why some people get depression while others don’t, why some people respond to one treatment and not another, or why one person will suffer from a form of depression that is less or more severe than another person. This lack of clear, empirical understanding comes at an awful price to victims of depression, as they encounter remarks from people that tell them to “snap out of it”, implying that they somehow can control the emotional crumbling and dark ideations that accompany the disease.

The consequence of all this is that it’s incredibly tough to create effective, lasting treatments for the disease if we can’t exactly track how the disease affects not only specific regions of the brain but the activity among individual brain cells in regions that may not have even been known to play an integral role in the disease. My layperson’s view is that treating depression currently is a bit like bringing in a car to the mechanic and telling him to fix it but there’s a catch – the mechanic can’t get under the hood to observe directly what’s wrong with the car. We suspect that the problem is with the engine but good luck with opening it up and peering into its pistons. So the mechanic attempts to work on the engine but indirectly, and whatever repairs are attempted may affect the engine but they may also have unwanted effects on the car’s transmission, muffler, timing belt, etc.

Fortunately, advances in imaging techniques like two-photon microscopy and fMRI are elucidating the activity of the depressed brain, allowing the previously impenetrable forest of billions of neurons to be explored, to see their pathways altered, their branches pruned by the disease. And scientists like Philippe Goldin and Kelly Werner are compiling biomarkers like DNA and brain blood flow activity to see if those biomarkers can help predict if people suffering from anxiety and/or depression will respond more favorably to cognitive behavioral therapy than to mindfulness meditation, for example. Dr. Deisseroth is using genetically engineered, photosensitive proteins implanted into rodents’ brains to control brain activity at the level of individual neurons.

Dr. M. Bret Schneider told me during our interview, “A real cure for depression is gonna involve being able to selectively affect those portions of the brain which don’t function properly in depression… But fathoming the huge number of possibilities in each brain with every brain being a little bit different than every other one, is gonna require individualized solutions and will be a scientific feat.” I suppose that with a disease as complex as depression, where one’s individual genetic makeup can influence the kinds of side effects one may experience with an antidepressant, it’s apropos that the future of treating and eventually curing it will entail personalized medicine. Until then, let’s hope that more people bring psychiatry into the research lab to study illnesses like depression, for it’s only through the methodical rigor of science that we have the best hope for curing depression.

Watch the Illuminating Depression television story online.

An image of a bioreactor being developed by OriginOil scientists.

Today’s episode of QUEST features our 10-minute TV story about efforts to produce biofuels from algae. In 1996, when the U.S. Department of Energy concluded its 25-year research project into the potential of algae as biofuels, its report concluded that the most cost-effective way to grow algae was in open ponds. With climate change and geopolitics prompting new research into the algae-as-fuel question, some companies are pursuing the open pond route, while others are looking into closed systems such as bioreactors. In our TV story we profile OriginOil, a Los Angeles-based company developing a bioreactor that looks like a miniature Christmas tree, complete with bright, colored lights. And we interview the CEO of Aurora Biofuels, a company based in the Bay Area city of Alameda, which is re-imagining open ponds, as well as trying to create strains of algae that are ideal for fuel production. Before becoming the CEO of Aurora Biofuels, Bob Walsh worked at the oil company Shell for 25 years. Here’s an excerpt of QUEST’s March, 2009, interview with Walsh, most of which didn't make it into the TV segment.

QUEST: What excited you about algae?

BOB WALSH: I ran oil products businesses for many years and understand the cost-competitiveness and the commodity basis of it. And what excited me about algae was, A, it’s renewable. B, you're using a feed stock of carbon dioxide, which is basically free. And finally, what excited me about this company, Aurora Biofuels, was the aspect of solving it end to end, not just the biotech (end of things), but also the engineering aspects.

Q: What has algae been grown for in ponds in the past?

WALSH: Algae’s been grown in open ponds for decades. And typically it’s been done with nutraceuticals – spirulina, which many people use as a protein pill. That is grown in open ponds, but not very cost-effectively because they haven’t had to be very cost-effective. They can charge $10 per pound.

Q: What would be the difference that you would be looking for in terms of cost-effectiveness, compared to what’s been done already?

WALSH: Historically, algae were just grown in an open pond and captured carbon dioxide (CO2) from the atmosphere and the sun. What we’re actually doing is injecting the CO2 we recover from a steel mill or power plant, to give the algae food. And we’ve engineered it to get better mixing, so it grows more quickly. And then finally, rather than drying the algae out, we actually do a wet extraction of the oil, which is much more cost-effective than drying it as they have historically done for proteins.

Q: So what price would you be aiming for, and what price can the algae be grown for now?

WALSH: Oil today has been around $50 per barrel. We believe we need to be competitive in the $50-60 range. And that’s what our final target is. I think oil will be $60-100 over the next 10 to 15 years.

Q: What would the algae biofuels facility of the future look like?

WALSH: You’ll situate it very close to a CO2 source – a steel mill or a power plant. It will encompass several thousand acres of barren land – because you want dry, barren land – and use salt water. And it would produce roughly 120 million gallons a year of useable fuel into the existing infrastructure.

Q: Can algae fuel actually make a contribution to our transportation needs?

WALSH: Algae can be a player. It’s going to take a lot of different solutions because of the different climates and things that you need for it. It’s also a trillion-gallon market. And so it’s not going to happen tomorrow. But certainly algae can be a 5- to 10-percent player in ten years, in the marketplace.

Watch the Algae Power television story online.

UCSF biologist Jeff Tabor holds up an ecoli culture designed to display the shape of a squid.

Synthetic biology portends big changes in our lives by ushering in a dizzying array of applications in everything from medicine to biofuels, environmental remediation to agriculture. Though many of these applications haven’t yet come on line, researchers are hard at work to synthesize new drugs and devices made from genetic parts.

For example, there’s an enzyme that exists in plants which makes methyl halides, a molecule which can be catalytically converted into gasoline and other chemicals. Imagine if you could put this enzyme-making gene into yeast, then you could brew the yeast to churn out the methyl halides and after some optimization of the production pathway, you could scale up production to pump out this carbon neutral gasoline precursor for use in today’s automobiles. This is the idea behind an innovative biofuels project that has taken off in the lab of Chris Voigt at UCSF’s School of Pharmacy.

Voigt and his team surveyed the genetic database for the presence of the gene that encodes for the enzyme that makes methyl halides. Lo and behold, the gene exists in plants as diverse as ice plant, which dots the northern California coast, bok choy and pinot noir grapes. After building a library of about 100 enzymes from these diverse plants, the researchers had to determine which of these would function best in the yeast. They zeroed in on an enzyme from ice plant and then used the tool of DNA synthesis to translate the gene for the enzyme that makes methyl halides into something that would work in yeast.

The remarkable thing about this project is that the researchers never actually touched any of the plants. They simply “Googled” a genetic database to find all the genes out there in plants that produce the enzyme that makes methyl halides. As Professor Voigt says, “it’s incredible that synthetic biology is something that could really unlock the potential of using organisms in order to produce fuels.”

Watch the video made by the Voigt Lab demonstrating the combustible property of their synthetically derived methyl halides:

QUEST on KQED Public Media. Video courtesy of
Prof. Chris Voigt, UCSF School of Pharmacy

Watch the Decoding Synthetic Biology television story online.

A LED flashlight powered by a battery made using five pennies.

Oops! Are we gonna get in trouble? In order to make our Five-Cent LED Battery we needed to sand the faces off 4 pennies. According to United States Code, TITLE 18, PART I, CHAPTER 17, § 331. Mutilation, diminution, and falsification of coins:

"Whoever fraudulently alters, defaces, mutilates, impairs, diminishes, falsifies, scales, or lightens any of the coins coined at the mints of the United States, or any foreign coins which are by law made current or are in actual use or circulation as money within the United States; or whoever fraudulently possesses, passes, utters, publishes, or sells, or attempts to pass, utter, publish, or sell, or brings into the United States, any such coin, knowing the same to be altered, defaced, mutilated, impaired, diminished, falsified, scaled, or lightened— Shall be fined under this title or imprisoned not more than five years, or both."

Gulp! Fraudulently? I don’t think we did it "Fraudulently." (Ahem) And I just want to say for the record that we did not force anyone to deface currency of the United States. In fact, if pushed came to shove I will say that we discouraged the practice and in fact actually pleaded with everyone at the Exploratorium, hoodlums that they are, to come up with another means of making a Five-Cent battery. But they brazenly went forward, stopping only briefly to maniacally cackle and call me names like "Goody Two-shoes" and thumb their noses at me. Needless to say they shamelessly went ahead with their outlaw ways. Oh, they are bad to the bone! We were as innocent as you all out there. I tried to stop them! That's what I will say! That or I’ll say that the "pennies" we were using were actually fake "prop" pennies that we got at the local novelty shop. Either way, you can't prove anything!

Now, if you don't want to risk being outside the laws of the United States, the Exploratorium has put together quite a fun project list of fun things to do and make. To the best of my knowledge, the majority of them won't get you in trouble with the authorities. They can teach you things like how to make musical instruments out of normal household junk, how to make a bottle blast off or how to build a motorized toy that dances, using a recycled CD and a DC motor. Really cool stuff!

Be good out there and stay out of trouble.

Watch the Quest Lab: The Five-cent Battery television story online.

Animals generally receive diets that are rich and varied.

Few images will stay as indelibly with me as the sight of a 500 pound grizzly bear devouring a horse bone while standing waist high in water. I should add to that the sight of a geriatric koala slurping his eucalyptus meal. In the aquatic realm, there's something ineffably captivating about watching an anemone's candy-pink arms wrap around its lunch of grain-sized krill.

Witnessing the feeding scenes firsthand, I marveled at the bewilderingly diverse array of mammals, reptiles, amphibians, birds and insects that are fed every day at zoos and aquariums worldwide. Fortunately, to facilitate the feedings and developments of diets, today there are tools like Zootrition, a software program developed by the St. Louis Zoo that allows for the nutritional evaluation and comparison of various diets. Then there's ZuPreem, a manufacturer of ready-made meals for exotic animals. A perusal of their web site reveals such tasty items as "Primate O's" (naturally preserved with vitamins C and E), canned monitor food (boasting nutrient levels comparable to "a mouse in a can"), bags of dry omnivore diet for the hungry bear or boar.

The upshot of this is that animals at facilities accredited by the Association of Zoos and Aquariums generally receive diets that are rich and varied, frequently monitored for the effect they have on the animals to whom they’re served. Not surprisingly, many animals at zoos and aquariums live longer in captivity than they would in the wild, not only because of the high level of care they get in captivity but also because they are safe from predation in the wild.

Jacquelyn Jencek, Chief of Veterinary Services at the San Francisco Zoo, shared with me an amazing story of how they greatly expanded the longevity of koalas with an intervention that has been emulated at other zoos throughout the nation. Most koalas in the wild don’t live past thirteen years of age, when their teeth have been ground down from years of eating coarse eucalyptus leaves and they no longer have enough dental surface to break down the leaves and extract their nutrients. Thus, even if they attempt to eat the leaves, they can still die of malnutrition. So the SF Zoo decided to help the koalas by breaking down dried eucalyptus leaves with a coffee grinder and mixing the powder with water and supplements, turning it into a solution that could be fed by vial to geriatric koalas at the zoo. The zoo first tried administering the eucalyptus solution to Clarry, who lived to be nearly 20 years old, and is now giving it to Clarry's son, Leo, and a few other koalas whose longevity attests to its success. According to Dr. Jencek, "they love the taste of it", and it's clearly good for them.

The story affirms for me the bond of trust that exists between the animals and the zoo and aquarium personnel who take care of them, and how there’s nothing cookie-cutter about feeding the animals and creating their diets.

Watch the Animal Chefs television story online.

The Stanford Linear Accelerator. Credit: SLAC.

Luckily, there is a particle accelerator right here in the Bay Area. Last year, I took an intrepid group down to the Stanford Linear Accelerator (SLAC) to learn more about the these giant expensive research labs.

SLAC maintains an extensive public outreach program. An extensive tour (mine was 2 hours with very in-depth exploration of the facility), public lectures, weekly colloquia, and even science competitions for high schoolers.

I was surprised to find a wealth of research beyond the typical particle colliding at the facility. Many researchers use the state of the art facilities to study basic elements of our life, including water.

On Tuesday, Anders Nilsson is discussing his research on water at SLAC, an in-depth look at some of the stranger properties of water: its high heat capacity, how it is more dense than ice, even insight on using water as a power source (by splitting it into hydrogen and oxygen). Water: The Strangest Liquid, Tuesday February 24th 730-830PM at the Stanford Linear Accelerator.

However, our continued economics woes are threatening physical science research. SLAC is getting the brunt of money cut, missing out on $23 million of requested funding. In response, SLAC laid off 125 of its 1600 employees and shut down its PEP-II collider last year.

SLAC Public Lecture Series
The SLAC Public Lecture Series opens the doors to the inner workings of SLAC for the local nonscientific community. Find out what SLAC is all about: the research, the facilities, and the people that make this a world-class research institute.

SLAC Colloquium
The intellectual watering hole for the entire laboratory, where you can hear talks intended for a general audience on a wide variety of subjects. The colloquium will be returning later this year.

SLAC Science Bowl for High School Students
SLAC hosts an annual Regional Science Bowl for teams of high school students. The Science Bowl is a question-and-answer competition with buzzers, judges, and time keepers for high school teams of 5 students and 1 faculty coach. This year's competition is on February 28th.

SLAC Tour Information
Tours of SLAC will be available again later this year. On the tour, you get an extensive look at the operation of the accelerator, including a peek into the Klystron Gallery.

It’s true that the majority of the work done there is in support of Department of Defense and Department of Energy programs. But contrary to what one might imagine, the scientists there are work that goes on there isn't ALL about figuring out how to protect the U.S. from Communism. The scientists here are chemists, physicists and engineers who are delving into everything from warhead electrical systems to enhanced mammography.

We’re led into the "firing chamber" to meet our explosives guy, Jon Maienschein, who has promised to blow something up for us. I’m excited. It’s hard to make a bad TV segment when an explosion is involved. If you watch television, you will see that many shows live and die by that rule. Maienshein is surprisingly mild-mannered for a guy who blows things up for a living. After interviewing him for about 30 minutes on camera, we finally had a very basic understanding of what’s happening during a detonation.

There are several different kinds of explosions: chemical, natural, mechanical and nuclear, electrical, astronomical, etc. The most common "artificial" explosives are chemical usually involving a violent, rapid oxidation reaction. The fine folks at LLNL demonstrated just such and explosion for us then gave us the super-cool, ultra-slow-motion footage that they shoot in order to study what actually goes on inside an explosion.

We see or hear about explosions practically every day on TV, the movies and in the news, most people have no idea what an explosion really is. What’s happening on the chemical and molecular level? And how do the people who know about explosives actually study explosions? And why is it necessary to understand this stuff? The whole thing is surprisingly complex.

Watch the Inside an Explosion television story online.

The 1992 'Peekskill' meteorite and its point of
impact in Peekskill, New York. Credit: "Pierre Thomas

The first thing I tell people is that I'm not a meteorite expert, but that I have a contact who is. This rarely discourages them from wanting to bring their rocks in for a look.

The first sample was brought in by a family who said they collected the chunk of iron from Lake Tahoe. This one actually looked promising to my mostly untrained eye: a fist-sized chuck of magnetic metal, with pits and holes and an overall melted look. I took some pictures to send off to our regional expert and told the family I'd call them to let them know what he said. The response to the pictures was pretty certain: it wasn't a meteorite, but a chunk of metallic slag. I was told that this is a common mistake; that often bits of slag from old foundries or other sources are taken for meteorites.

The second sample brought to me didn't really strike me as a meteorite, by appearance. It was metallic, but not magnetic; it was pretty heavy for its size; it didn't have any obvious signs of melting, and no real pits or holes-other than one, deep, tunnel-like hole the width of a finger. It didn't appear jagged or shrapnel-like, as fragments from an exploding metallic meteorite often do. Finally, it had wide, flat facets that looked much more like the result of natural rock cleaving as pieces of Earth's crust break apart.

I went ahead and performed a density measurement on the sample. It was pretty heavy, so our sensitive balance scales wouldn't handle the load. Instead, I resorted to our "learn your weight on other planets" scale-the one that tells you how much you would weigh on the Moon, Mars, and other planets, in addition to your Earth weight. (I found this scale useful when I had a package to mail and needed to know the weight; by selecting the Moon weight of the package, I would pay only one-sixth the normal Earth rate!)

The double-fist-sized sample was 11.3 pounds, which converted to 5126 grams. Then, I selected a graduated beaker from our lab, filled it with water and submerged the sample. Reading the difference in water level with and without the sample, I measured a volume displacement of 750 cc. So, the density-mass divided by volume-turned out to be about 6.83 grams/cc. That's twice the typical density of silicate-type rocks (stone), and fairly close to that of pure iron.

I sent the owner off with my appraisal that the rock didn't present the appearance of a meteorite, and though the density was in neighborhood of that of iron, the appearance (black, inside and out) and non-magnetic nature suggested some other metal or metal-stone mixture. As always, I encouraged him to seek an expert appraisal.

Let's face it, all rocks found on Earth are ultimately of extraterrestrial origin-though what we regard as Earth rock has been on Earth for many billions of years, and shaped, reshaped, and metamorphosed by eons of weathering and geological activity. Meteorites, then, are only the newcomers….

When I was assigned to work on our QUEST story on nanotechnology, I braced myself for the complex terrain ahead. The focus is on the public policy implications of the surge in consumer goods containing nanoparticles. And just how big is the market for nano-manufactured goods? According to the Project on Emerging Nanotechnologies, a partnership between the Pew Charitable Trusts and the Woodrow Wilson International Center for Scholars, there are hundreds of products available to consumers that contain manufactured nanomaterials. They run the gamut from tennis rackets to toothpaste to air purifiers and even stuffed animals which contain antibacterial nanosilver. Lux Research projects that the worldwide market for nano-manufactured goods will exceed 2 trillion dollars by 2014.

Meanwhile, the federal government has been criticized for failing to regulate more stringently the use of nanoparticles and for not investing enough dollars to study the effects of their exposure. Even when the federal authorities do act, like when they ruled that germ-killing products laced with nanosilver must be registered as pesticides, it makes you scratch your head at how outdated some of our environmental laws are and ill-equipped to deal with materials that came online after the laws were written.

The nuts and bolts of producing this story were challenging as well. To lay out the public policy debate, we needed to get opinions and facts from an environmental organization, the federal government and a firm that is actually manufacturing products at the nano-scale. I was also fortunate to get access to Kent Pinkerton and his colleagues at UC Davis, who are studying the exposure effects of quantum dots and carbon nanotubes on rodents. Special thanks goes to my Associate Producer, Jenny Oh, for securing an important interview with Dr. John Howard, the director of the National Institute for Occupational Safety and Health. As I was about to commence my interview with Dr. Howard, I ran through with him the list of questions, including one about respirators and whether they would adequately protect exposure to materials that are thousands of times smaller than the human hair. Without missing a beat, Dr. Howard grabbed his pen, asked me for a sheet of paper and drew a sketch of a filter lattice, explaining how yes, thanks to Brownian motion, the tiny nanoparticles would be moving around so wildly that they would bounce off the surface of the lattice. Bigger particles, on the other hand, may get through the lattice.

Discussion about nanotechnology, its benefits, its risks, the knowns and unknowns will continue for some time. Perhaps QUEST will revisit nanotechnology as new breakthroughs emerge and science reveals more clearly how nanoparticles affect the environment and living organisms.

Watch the "Macro Concerns in a Nano World" TV Story online, as well as find additional links and resources.

The new FOCE experimental chamber being developed by MBARI scientists.

The scientists at the Monterey Bay Aquarium Research Institute (MBARI) are already well-known for uncovering some of the most extreme marine animals in the deep sea, like the incredible vampire squid. But recently, they're using their unique blend of biology and engineering to study one of the least-discussed impacts of climate change: ocean acidification.

When we hear about climate change, we tend of think of the atmosphere – and for good reason. But as MBARI scientists describe, the oceans are a key part of the process. The ocean acts like a giant sponge, absorbing carbon dioxide emissions from the air. And as we add more and more CO2 to air by burning fossil fuels, the ocean is absorbing it. On one level, it's done us a big favor. Scientists say that we would be experiencing much more extreme climate change were it not for the ocean's ability to remove the heat-trapping gas.

However, the carbon dioxide that the ocean absorbs is making the water more acidic. This isn't the first time that the oceans have become more acidic. But as is the case with many impacts of climate change, it's the rate at which acidification is happening that worries scientists the most.

As you can probably guess, the ocean is an incredibly complex system. So ocean acidification poses an interesting question to scientists: what will the impacts be on marine species and ecosystems? What they know already is that there will be winners and losers in more acidic waters. Some creatures may do fine, while others won't be able to adapt in time. Either way, food webs may feel the effects – including webs involving species that humans depend on , like salmon.

Another major concern has to do with marine animals with certain kinds of shells – known as "calcifiers." Corals, clams and others all use carbonate in the water to build their shells out of calcium carbonate. But ocean acidification reduces the amount of carbonate in the water, making it more difficult for them to make shells. That could be devastating for coral reefs, who are already facing a number of stresses.

Even if you're an animal without a shell, ocean acidification could make things difficult. Scientists are studying how much stress this could put on animals that can't regulate their internal pH, or how it could affect the larvae or reproduction of certain species. MBARI scientists are hoping that the flume they are developing to conduct FOCE experiments will help researchers answer some of these questions.

Check out the whole story – watch the "Acidic Seas" audio slide show online.