As a pediatric ophthalmologist, there are times I have to deliver some pretty difficult news for patients and families affected by genetic disorders of the eye.
There are often no treatments, much less cures. Families come to me and I have to tell them, "Your child is going to lose vision, slowly and inexorably, and he or she may end up completely blind."
It can be devastating.
Shortly after arriving in Madison in 1999, I decided to focus my research on developing technologies to help these families.
We knew then that many genetic disorders result in the loss of critical cell types in the retina known as photoreceptors. These light-sensing cells slowly become dysfunctional and then die.
Unfortunately, the eye is incapable of replacing photoreceptors, and no practical source of new human photoreceptors was available.
Then I learned about UW-Madison researcher Jamie Thomson’s pioneering work in stem cells. We figured there must be a way to take these very undifferentiated stem cells, which are kind of little pieces of human-cell clay, and mold them into spare parts for the retina.
Over the course of eight or nine years, we developed methods to grow photoreceptors and even whole human retinas in a laboratory dish, and we can do so in an unlimited fashion from any person. This was a defining moment for us.
But having spare parts is only half the battle – we next had to ask whether they could actually be used to reconstruct a degenerated retina.
Can we take these brand-new photoreceptors out of the wrapper and put them in a patient, and will they connect with other retinal cells and ultimately send a visual signal to the brain?
That’s a part of the problem over which we have much less control.
If the downstream retinal circuit is a mess, putting fresh, new cells in there isn't going to be of much help. In other words, a new light bulb is of no use if the socket wires are cut. Fortunately, the socket wires appear to be in reasonable working order in many patients with photoreceptor degenerations.
Some tough work lies ahead.
I use the analogy of the Wright brothers. They weren’t looking to fly across the Atlantic non-stop and serve two meals on the way. All they wanted to do was glide off a hill and not hurt themselves. If an investor told them “I like this flying idea, but I’m giving you a year to cross the Atlantic or we’re pulling the plug,” where would human flight be now?
The same goes for our work. We have to accept that these are hard problems, and we are going to get more things wrong than right in the beginning. But I am confident that, with diligence and collaboration, we’ll get there.
My research wouldn’t be close to where it is now if I hadn’t been in Madison. When I was starting out and struggling to understand this new field of science and medicine, I was able to learn from UW-Madison’s giants in the stem cell field.