by Peter Hansen
uch research has been done on the fundamental unit of lifethe cell. With the help of powerful electron microscopes, scientists have learned the complex structures within the many different types of human cells. And by observing which nutrients are transferred from cell to cell, or measuring the changes in neurons electrical charges as signals are passed between them, scientists have a pretty good idea of what cells are doing.
But what exactly happens at the cell membrane to allow nutrients and signals through? And what happens inside a good cell to make it go bad? Answering these kinds of questions could help develop better treatments for or even prevent many different diseases. As strong as electron microscopes are, the static images they produce cant tell the whole story; cells cant survive in a vacuum, which the machine needs to do its work. So seeing whats going on inside a living cell requires a different kind of instrument.
The main tool Yakovlev uses is optical spectroscopy, a method used to identify and quantify matter by observing how it absorbs, emits, or scatters light. Using light as his tool offers the potential of non-invasive study of cellular activities.
You could look at living tissue without inserting probes and things like that, says David Heathcote, a professor of biological sciences collaborating with Yakovlev. Just using light to look at changes in the structures of the membranes or different parts of the cell and getting an idea of whats going on without putting in dyes or anything else.
Yakovlevs light source is a Cr4+:forsterite laser (a laser composed of forsterite doped with chromium). As he scans a cell with his laser, getting information about whats inside, a sort of picture emerges. The smaller the size of his laser beam, the higher the resolution of the picture. So far, the best resolution is limited by the diffraction of light to about 200 nanometers, or billionths of a meter.
But even that tiny laser, with the intensity of a trillion watts per square centimeter, could easily destroy the thin cell membrane and the organelles inside, without doing anything that is useful, Yakovlev says dryly. The key is to keep the exposure time short. Ultrashort, to be exact.
How can he generate such short pulses? In a typical laser an active material is somehow excited and is capable of emitting quanta of radiation within a certain range of a spectrum, Yakovlev explains. This is known as stimulated emission radiation, which is the ser in the abbreviation laser. By putting a set of mirrors around the active material, light can be cycled back and forth through the active material, resulting in light amplification, (the la in laser).
Typically, laser operates in many modes. Each mode is characterized by its individual wavelength within the gain spectrum of laser material. By introducing some external mechanism that is able to synchronize all these modes, one can generate ultrashort pulses, whose duration is limited only by the bandwidth of the laser material.
Yakovlev then offers a somewhat less scientific explanation, making a comparison to Darwinian evolution. You just have some kind of mechanism which says short pulses are better for survival, he explains. So you can just let this system develop itself and it will generate short pulses. So thats the beauty of it: the system by itself selects shorter pulses as a way for survival.
In addition to high resolution, images must be created at a high rate to capture the movement of signals or nutrients within cells. Yakovlev is able to create about 100 images per second, which is more than fast enough to capture activities such as cell reproduction. But if youre looking at transfer of signals from one neuron to another, its incredibly slow, because one pulse is formed within one millisecond, so you need kilohertz repetition rates; you need at least 1,000 frames per second in order to catch these events. So far, no one has been able to achieve that rate, he says.
Its not only a problem of optics or biology. Its basically getting your data fast enough, so its an engineering problem.
Another tool Yakovlev uses is Raman spectroscopy, with which he can get information about vibrational properties of molecules.
This way you get a fingerprint of your molecules, he says. Thats how you extract information. How do you know what the particular molecule is doing? You look for changes in the vibrational spectrum and, if you have a clever way to relate these changes to the variation of molecular structure, you can analyze molecular motions and structure changes associated with a particular biological process.
But its a complicated task and nobody, so far, has been able to solve this problem, figuring out exactly what all the components of the cell are doing. Thats the nature of research: you start from something and try to get as much as possible.
Yakovlev also hopes his work will lead to better ways to diagnose and treat cancer. With a clearer picture of how cells operate, drug makers could design more effective treatments. Something goes wrong with your cellaccording to latest theories its most likely DNAand it results in protein malfunction. Were trying to find a better way to look at this, Yakovlev says.
Or lasers could someday remove cancer cells from healthy tissue directly. You basically kill the source of future disease. There are plenty of ways to use lasers.
A current limitation with Yakovlevs optical techniques is that his lasers can only penetrate tissue to depth of a few millimeters. Someone has to come up with a very smart idea. I dont have this idea yet.
Still, Yakovlev is hopeful that his work and others will show results within 10 to 15 years.
I dont see the reason why a cure for cancer cant be found within our generation.