Harvard researchers publish MRI images of genes in action in the living brain

Biologists have just confirmed what poets have known for centuries: eyes really are windows of the soul—or at least of the brain. In a new study published in the April 2008 print issue of The FASEB Journal (http://www.fasebj.org), Harvard researchers describe the development of gene probe eye drops that—for the first time—make it possible to monitor and detect tissue repair in the brain of living organisms using MRI. Current methods involve a risky, invasive, and relatively slow process of penetrating the skull to extract tissue samples and then examining those samples in a laboratory.

“We hope our study provides a tool for better treatments of neurological diseases, diagnosis, prognosis during therapy, and improved delivery of therapeutic agents to the brain,” said Philip Liu of Harvard, one of the researchers involved in the study. Liu also said that more research is necessary to determine exactly how these gene probes reach brain tissue.

In this report, Harvard researchers describe how they link a relatively common MRI probe (superparamagnetic iron oxide nanoparticles) to a short DNA sequence that binds to proteins in cells responsible for brain tissue repair (glia and astrocytes). Then, researchers used the eye drops on mice with conditions that cause “leaks” in the blood-brain barrier. When the animals’ brains were scanned using MRI, brain repair activity was visible. Glia and astrocytes help repair brain and nerve tissue, and have a role in numerous diseases and disorders that cause at least microscopic breaches in the blood-brain barrier, including traumatic brain injury, multiple sclerosis, stroke, cardiac arrest, and glioma, among others. Furthermore, the researchers believe that the probes may also help diagnose thinning of vascular walls in brains, which occurs as Alzheimer’s disease progresses.

“When people are sick, the last thing you want to do is puncture their skulls for a biopsy,” said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal, “but sometimes this is unavoidable. These probes of genes in action go a long way toward ushering in an age where extracting brain tissue to identify a disease will seem as crude as when doctors measured skulls to diagnose a mental disease.”

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Do our feet deceive us more than our eyes do?

Researchers have known for some time that people are surprisingly accurate at visually judging distances to objects as far as 25 meters away. If you're allowed to briefly look at an object up to that distance away, then blindfolded, you'll walk right up to it with great precision. If you walk halfway, you can throw a ball the remaining distance, again, quite accurately.

But in 2000 Marla Bigel and Colin Ellard attempted a simple replication of the study: instead of viewing the object, volunteers were led blindfolded to the object and back, and asked to walk back to the object again. Now, instead of accurately walking the distance, they systematically overestimated the distance to the object. Could our feet deceive us more than our eyes, even when we're simply asked to retrace a path we've just taken?

There's another possible explanation: maybe being led is what causes the deception. In a new study, Ellard and Sarah Shaughnessy asked 30 volunteers to walk blindfolded along a roped-off 10-meter pathway. They could use the ropes to guide themselves, but were never led by researchers. As before, they walked the distance to the object, then returned to the starting point, and finally attempted to walk the same distance again. Another group of volunteers simply looked at the object and then tried to walk to it blindfolded. Here are the results.

Now everyone was very accurate at pacing off the distance, whether they had walked it off or viewed the target first. It appears that the act of leading a person blindfolded over a distance systematically skews their perception of the distance, but when they walk unassisted, people are able to accurately judge distances, even while blindfolded.

So if both viewing the object and walking to an object result in accurate distance estimates, then which method takes precedence? In a new experiment, Ellard and Shaughnessy had volunteers both walk to the object and view it -- but the object was a different distance from the viewer each time. So the object might have been 6 meters away when the distance was walked, but then it would be viewed 8 meters away. As you might expect, responses were biased towards the most recent distance, whether the object was viewed or walked to. But responses were biased more to the viewed object. When the viewed object was seen last and 8 meters away, viewers were just as accurate as when they had only seen the object at that distance.

So humans appear to be more comfortable using the visual system to judge distance than using the motion of their bodies. Researchers had initially found that that people were very bad at judging distances when blindfolded, but then realized that people were preoccupied with worries about whether they'd bump into a wall -- so all the experiments discussed here were conducted outside, in an open field.

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The 10 Craziest Scientific Experiments Ever Conducted

Science is all fine and good and has provided us with countless modern wonders, from laser beams to space flight to ultra absorbent, soft-as-a-cloud toilet paper. But lest we forget, the road to Charmin Ultra isn't just paved with red, raw asses. Over the years more than a few scientists have strayed from the path of useful research into crazy as a shithouse rat research.

Perhaps none strayed further than these:

Wilhelm Reich Studied How Sex Affects Weather

A psychoanalyst who in the 1940s who was really really focused on sexuality, Wilhelm Reich believed that the human libido had its own kind of crazy kung-fu type chi energy. He called it orgone, because "humptricity" was the name he was saving for his rock band.

He built orgone accumulators, boxes made of metal, steel wool and various other pulled-out-of-his-ass materials so that people could sit inside and absorb all that sexy orgone goodness. Orgone was so awesome it caused weather, the sky being blue, gravity and sexuality. So you really liked sex, Wilhelm. We get it.

But everything good has a downside and apparently orgone radiation was pestered by an opposite force (called deadly orgone radiation) that caused plants around Wilhelm's lab to die and menacing clouds to form. We wish we were making this up. Wilhlem made it up, but we didn't. Anyway, to combat the deadly orgone, Wilhlem did what any rational man would do, he build a "cloud buster," a bunch of tubes that had cables leading to water. He pretty much just got crazier from there.

Laugh all you want, but Wilhelm talked Albert Einstein into studying his orgone accumulator, and the pair spent some time measuring the device to see if it could in fact draw energy from Einstein's boner. We're going to go out on a limb and say that Einstein was drunk off his ass during their entire project.

Charles Claude Guthrie and the Two-Headed Dog

Charles Claude Guthrie wasn't exactly a cackling, evil madman, but due to the constraints of the time he lived in (early 1900s), being all full of crazy shit and whatnot, the man performed a couple of experiments that today would get you shunned by all but the maddest of scientists.

Guthrie was instrumental in developing modern day transplant practices, and while that would be a pretty cool legacy for any man to have, he was also probably the first guy to sew the head of one dog onto another dog, at least for business purposes.

And just to clarify, that wasn't a head transplant. He made a two-headed dog, possibly as a first step towards creating Cerberus, the three-headed dog of the Greek underworld that you probably saw in the first Harry Potter movie.

Hwang Woo-Suk's Mammoth Mistake

Hwang Woo-Suk, a Korean scientist who made some waves with apparent breakthroughs in stem cell research, also happened to be a massive fraud. In 2006, he was indicted on embezzlement and bioethics law violations linked to faked stem cell research. Rather than blow the money on long, sleepless weekends in Vegas, he spent over a half million dollars in private donations trying to clone woolly mammoths.

And while that may be bad enough already, apparently he thought involving the Russian mob, just to take this up a notch on the "what the fuck" belt was a good plan, and gave a chunk of that donated cash to the Russians in exchange for some organized crime-related extinct animal cells (something we didn't know mobsters trafficked in, and in fact would not have believed it had it come up in a movie).

While stem cell research could lead to breakthroughs in the treatment of numerous diseases, it will not apparently lead to Hwang's vision of a woolly Jurassic Park.

Kevin Warick: Cyborg

Kevin Warwick, a British scientist and professor of cybernetics, has the distinct honor of being one of the few insane experiments currently still in progress throughout the world. This man has a super hard-on for robots, apparently, so much so that he's endeavoring to be the first man ever to become a cyborg.

To this end, Warwick had a chip implanted in his arm that allowed him to control small, mostly uncool things around his home. He could turn on lights and open doors. Basically the kind of shit having at least one finger will allow you to do now, but lazier.

A couple years later, a more advanced chip was linked to his nervous system to the end of using it to control a robot arm. In a fun PR stunt, they implanted a similar device in Warwick's wife and the two of them engaged in the "first purely electronic communication experiment between the nervous systems of two humans" across the internet, whatever the hell that means. We suspect file sharing of porn was involved.

Paracelsus Theorizes the Dung Baby

Paracelsus, who once went by the name Philippus Theophrastus Aureolus Bombastus von Hohenheim, which he made up himself, was an alchemist and physician back in the 1500s, and is responsible for some of the earliest work in toxicology and psychotherapy. Apparently he was the first person to ever mention the unconscious in a clinical manner, good for him. He also wrote about how you could create a homunculus, which is basically a tiny man you make yourself. That's right.

In fact, this little dude would be better than making a human the old fashioned way (via sweaty, grunty humpage, for you naive types) because you could keep it pure, since Paracelsus figured a real baby is all corrupted with those female juices, and who wants that garbage?

No, according to Paracelsus' writings, the only way to create a pure man via homunculus was to take some semen, put it in a bottle, and submerge it in horse shit for 40 days. Then, when the tiny man you've created starts to form and wiggle around in the bottle, he said you needed to feed it blood for 40 more days.

Hey, remember when we said the guy was a physician? Yeah, he was treating people this whole time. This is another reason why if you got sick in the 1500s, you were probably better off just staying home and rolling the dice.

Duncan MacDougall Could Guess Your Soul's Weight

Duncan MacDougall is one of the shadiest sounding doctors we've ever come across, and seems like the kind of guy who liked to play games like "Drink This Bubbling Liquid" and "Smell my Ether Soaked Rag," both of which we learned were unfun after playing a couple rounds with the man who sold bikes around the corner.

In the early 20th century, MacDougall theorized that the soul had weight. His experiments even came up with a number, 21 grams, which is where the title of that movie came from. What experiments you ask? The experiments where MacDougall took six patients "in the process of dying" and weighed them.

Being a profound scientific mind, there's not much written about who these people were or why and how they were dying. It's just enough to know that in their last moments, probably while they were hoping for a miracle, or maybe CPR, they were getting rolled onto a scale like deli-sliced meat at the market.

MacDougall also took the time to replicate his experiments with dogs. Fifteen dogs, in fact, which were apparently uncooperative when it came to dying of natural causes, so he had to help them along towards doggy heaven.

Although, according to his experiment, while humans lost anywhere from no weight because they died too quick for him to adjust his scale to several ounces at death, dogs lost nothing and therefore have no souls, which by our calculations means Guthrie's two-headed dog had twice as much no soul as a regular dog and was therefore evil to the core.

Johann Conrad Dippel Was Basically Frankenstein

In 1673, Johann Conrad Dippel was born in castle Frankenstein. Seriously. We could probably just stop talking now, but what the hell, let's go for it.

Thought to be the inspiration for the good doctor from Mary Shelley's book, while in the castle he spent his days practicing anatomy and alchemy. Naturally, it's said some of this anatomy involved boiling various body parts in large vats to make some kind of mad man stew. Rumor has it he also tried his hand at moving the soul from one corpse to another, possibly with a funnel, a hose and a lot of lubricant.

There are also various rumors of grave robbing that lead to his association with the Frankenstein story. Whether any of that is true is up for debate, but he did get run out of town for whatever the hell he was doing.

He is also credited with inventing Dippel's Oil, a tasty tonic made from bones, blood and various other fun animal products distilled into what was supposed to be the Elixir of Life, but apparently was just a foul-smelling stimulant that probably gave people mad cow disease.

Nikola Tesla: The Crazy Edison

Nikola Tesla made mad scientists the glamorous kooks they are today. Without him, all those reanimated corpses and turtle babies would be relegated to back alley practices with no one batting an eye. In his life, Tesla made great contributions to research into electricity and electromagnetism, yet also did things that moved him close to Batman villain territory.

For one thing, Tesla had a few quirks. He had an intense fear of dirt and germs. He also disliked anything round, and was disgusted by pearl earrings. He would only stay in hotel rooms with numbers divisible by three and had a curious obsession with pigeons. He hated fat people and would not speak at conventions without his invention, the Tesla coil, which was a giant lightning-shooting transformer made famous in many sci-fi games and films, always buzzing in the background.

When not shooting lightning for kicks, Tesla was pondering other ways to use electricity, among them the theoretical creation of a superweapon particle beam that would be able to shoot down "10,000 enemy planes at a distance of 200 miles." He also put thought into anti-gravity airships, time travel and a thought photography machine that would take pictures of things from your imagination and display them on a screen. We're pretty sure if we hooked Tesla to that machine, we'd just get the same image of the Earth being shocked to shit by huge bolts of electricity, again and again.

Michael Persinger and the God Helmet

Michael Persinger is a cognitive neuroscience researcher who apparently got bored with all that, and instead put effort into turning a snowmobile helmet into a doorway to God Himself.

Aptly named the God Helmet, Persinger's invention basically fucks with your brain using magnetic fields in your parietal and temporal lobes. The result is the feeling that Jesus may be right on the verge of pantsing you or just sort of hanging out for no good reason. More than 80 percent of participants report feeling an ethereal presence in the room which they say is either God or a dead loved one, but hopefully not Satan.

The point behind zapping someone's brain until they feel like God is in the room is probably really cool and sciency, it seems to us there are only two possibilities: either this will become a party game that kicks the ever-loving crap out of Ouija boards, or else Persinger has actually opened up a portal to the realm of the dead.

Persinger has gone on to try to explain damn near all unexplained phenomenon as being caused by the same kind of electromagnetism (just as the show Lost seems to be doing). As you might expect, he came to the conclusion that UFOs were caused by seismic faults. Seems these faults create EM fields that can cause hallucinations "based on images from pop culture," which doesn't explain why they are always seeing aliens coming at the instead of, say, Harrison Ford or that other guy from Wham!.

Thomas Midgley Jr. Tried Really Hard to Destroy the World

First of all, Thomas Midgley Jr. was responsible for leaded gasoline, which he created for General Motors. This is the gas you can't get any more. Why? Because lead is fucking poisonous, that's why.

In fact, while working on his leaded gasoline additives for GM, Midgley managed to give himself lead poisoning. Over the course of its first year in operation, ten employees died of lead poisoning and many others became ill. Naturally, GM didn't like this. Not because people were dying, but because the work was taking too long, probably because of all the people dying. So, in the name of good old-fashioned American efficiency, they made a new plant and started using a faster, more dangerous method.

Within two months the new plant had a slew of new lead poisoning victims suffering hallucinations and insanity, as well as five more deaths. Midgley did the only responsible thing. At a press conference, he washed his hands in the leaded mixture and breathed in the fumes for a full minute to show it was safe. Thus, for decades cars would continue to pump Migley's poison into the air.

But Migley wasn't done. When General Motors told him they needed a chemical to use as a refrigerant, he invented chlorinated fluorocarbons. CFCs. Decades later, long after his death, the world would find out these CFCs were making a hole in the ozone layer. His leaded gasoline, meanwhile would be banned in 1973, only after vehicles had pumped mind-boggling amounts of lead into the air, killing thousands and permanently damaging tens of millions more around the globe.

Midlgey ended up severely disabled by polio and his final invention was a series of pulleys that he used to help himself in and out of bed, proving that even disease was no match for his inventive mind. Some time later he got stuck in his pulley system and died of strangulation, a death that, while tragic, probably prevented him from inventing some chemical that would accidentally melt the flesh off all our bones.

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