In this note I will try to illustrate how the terms theory and hypothesis differ. To do this I shall use a recent article from New Scientist: "Low-power laser may keep blindness at bay", 16 January 2013 by Michael Slezak, Issue 2900.
Put simply, an hypothesis is a statement about something that may be true or false. For example, I could hypothesise that 'smoking increases the chance of getting lung disease.' My research task would then be to test this statement by looking for evidence in one way or another. Now, you may arrive at your hypothesis in many ways, commonly though: intuition, guessing or partial evidence. In medical science we might get an idea for a test to verify the hypothesis but obviously, in medical things we must at least be careful that what we propose won't do any harm.
Typically, with a hypothesis you don't understand why it is true, the mechanism. That is its one thing to suggest smoking causes lung disease and quite another to explain the causal mechanism. On the other hand with a theory, we do have a suggested causal mechanism, an explanation, and such theories predict certain things which we can look for to verify the theory. For example with smoking we might predict that the causal mechanism is narrowing of the arteries and therefore we look for that evidence in patients. Now an example.
IMAGINE the horror of being told you are losing your sight and that nothing can be done to prevent it. This is the reality for millions of people with age-related macular degeneration (AMD). But a novel laser treatment for AMD gives hope that this leading cause of blindness in the West could one day be preventable. As we will see later, unpublished results from a pilot trial have left researchers scratching their heads as to exactly how it works, indeed, the findings also challenge ideas about the basis of the disease.
AMD corrodes the macula, a part of the retina with the highest density of photoreceptors. The disease leaves people with a gaping hole in the middle of their vision, making reading and recognising faces difficult or impossible. There is no treatment for the most common form of the disease (dry AMD), but drugs that slow its progression are available for the rarer, more aggressive form (wet AMD).
In most people, the condition starts with unusually large deposits of extra-cellular debris called "drusen" littering the retina. Drusen, which consist of proteins and lipids, are supposed to be cleared away by the retinal pigment epithelium (RPE) cells. But as those cells age they become less effective at doing that.
The exact cause of what happens next is not well understood. Either because of the extra drusen, or as a result of whatever is damaging the RPE cells in the first place, the RPE cells become starved of oxygen. As they die off, they stop providing energy to the photoreceptors, causing them to die too. This is a serious problem as the density of photoreceptors is highest in the macula, so any loss noticeably affects vision.
As early as the 1970s, there was some indication that laser treatment cleared away the drusen, but this did not come with an improvement in sight. In some cases, trials were even halted for fear they were making things worse. This is unsurprising as the lasers used were high energy and made visible burns on the retina. But today's more sophisticated, low-energy lasers offer more subtle options.
In 2010, ophthalmologist Robyn Guymer at the University of Melbourne's Centre for Eye Research Australia conducted a pilot trial with 50 volunteers who were in the very early stages of the disease, with some build-up of drusen. They each had treatment in one eye with a specially designed laser.
After treatment, the majority of the participants saw benefits - a reduction in the amount of drusen, an improvement in their sight, or both. In lab tests, some participants were able to notice small differences in the intensity of light indicating that the retina had regained some of its function. "The sensitivity of the retina improved in the spots that were most at risk of running into trouble," says Guymer. "There's been no other intervention where you can improve the function of a person's retina."
So why should lasering the already embattled RPE improve things? One THEORY is that the cells are so tightly bound that they never divide and regenerate, eventually becoming less effective at removing drusen. If the laser shot through that layer, killing some of the cells and breaking up the tight bonds, it may have allowed new RPE cells to be created. The laser should be able to do this because, rather than a uniform beam, it is made up of thousands of little beam spikes which turn its target into a pin-cushion. It kills a smattering of individual cells but leaves enough healthy cells in between to kick-start the regeneration of the RPE.
This cannot be the whole story, though. When Guymer conducted the pilot study she treated only one of each volunteer's eyes in order to use the other as a control. To her surprise, among those participants who saw a reduction in the drusen, most of them experienced the effect in both eyes. "It's a little hard to explain how the other eye is affected by the [rejuvenation] mechanism," says Guymer. It seems something else is triggering a response in both eyes.
Guymer reckons the immune system might be responsible. To protect the eye from potentially damaging inflammation caused by an immune response, it usually sits outside the immune system's radar. Unfortunately, this means that the drusen are also "in an immune privileged position", says Guymer, hidden by a tight layer of RPE cells. She thinks that when the laser kills some of the RPE cells, it effectively alerts the immune system to the presence of the drusen, triggering a double-whammy clean-up of the debris by both the immune system and the newly rejuvenated RPE cells. "That's not proven," Guymer stresses, "that's just the working HYPOTHESIS."
Philip Rosenfeld at the Bascom Palmer Eye Institute in Miami, Florida, is excited by the results and says the immune explanation is plausible. "You can come up with a lot of explanations but the most likely HYPOTHESIS is that something is being stimulated in the immune system that's been transferred to the other eye," he says.
Although still a long way off, Guymer sees a future where the new laser is used as a preventative measure in people at high risk of AMD, in a similar fashion to the way heart attacks are prevented by treating blood pressure. "Ultimately, if your parents had AMD, you'll have a genetic test and if you've got the gene you'll have this laser and you won't get the disease. That's where we would like to head. One lasering, perhaps once a year, for those who are genetically at risk," she says.
If Guymer had her way, this approach would be just the start. She imagines a time when people at genetic risk simply get vaccinated so their body recognises the drusen and clears it away. "We just need to trigger the immune system to do a better job cleaning up that debris."
