Philip Nelson, a physics professor in the School of Arts & Sciences, stands in front of a blackboard in the David Rittenhouse Laboratory.

“Do you see my secret message?” he asks.

The blackboard is scrawled with numbers and equations, the secret message hidden somewhere within them. He relates this to optical imaging.

“You look through a microscope and you see all sorts of junk,” Nelsons says, “all sorts of distracting stuff there that you don’t want to see. Wouldn’t it be great if you could tag the stuff that you want to see in some way that it’s the only thing you see?”

Then, he turns off the lights in the room and flicks on a small, ultraviolet bulb. In glowing letters, the word ‘hello’ appears. It was there all along, he says, “hidden in the visual noise.”

Nelson calls this an “experience of nature,” and his course, “Physical Models of Biological Systems,” and recently released book, “From Photon to Neuron: Light, Imaging, Vision,” are full of similar ones.

“From Photon to Neuron,” which was published this month, delves into a modern revolution, starting from the early 20th-century discovery that photons—the basic units of light—are both particles and waves. Recently, scientists have begun to exploit this duality to hone their techniques of optical imaging, including the fluorescence microscopy method that inspired the blackboard demonstration.

Thanks to this optical revolution, scientists can now more precisely examine chromosomes using spectral karyotyping to identify abnormalities that may otherwise have gone undetected. They can also capture a level of fine spatial detail that all textbooks said was off-limits—until recently.

Nelson cited a recent Penn study wherein, using real-time fluorescence illumination, surgeons were able to see bits of cancer they missed while performing brain surgery so that they could go back in and remove it during the same procedure.

The photon picture is also essential to understand the brand-new field of optogenetics, which uses light to control cells in living tissue. It’s now possible, Nelson says, to reach individual cells and turn a single neuron on or off in the middle of an intact, living brain, without affecting the thousands of other neurons surrounding it.

He hopes that, using the skills they gain through his course, students will be able to participate in this ongoing revolution, applying the newest techniques to their own research problems. Development of the book, which was supported by the National Science Foundation, the University of Pennsylvania Research Foundation, and SAS's Research Opportunity Grant program, will allow others to teach similar courses elsewhere.

Human beings have 100 million cells in the back of each eye, many of which can send a nerve signal to their brains when hit by just one photon, the smallest possible amount of light.

“That’s the absolute physics limit to how sensitive any detector can be,” Nelson says. “It took forever for humans to invent laboratory apparatus that sensitive, and yet our own eyes have already been there for millions of years.” 

Through bright minds, scientific modeling and exploration of the strange quantum properties of light, scientists are continuing to push imaging techniques to new capabilities.

“There are things of the spirit and there are things of the world,” Nelson says. “I think it's great when you need one in order to get the other. There are so many situations where the beautiful things are not obviously important, or where the important things are not obviously beautiful. My students get energized when I can show them the intersection, where the fascinating, weird parts of science have direct practical value.”