Turning Stem Cell Biology into Stem Cell Medicine

They asked me to talk with you about what
floats my boat. What gets me to do what I do. I’m going to start by telling you why all
I want to do is stay in bed with covers over my head. Let me tell you about the typical life of
a university scientist. Everything that happens in our lab we’re responsible
for. Not just the ideas but raising the money. Every technician, every student, every post
doc, our own salaries, we have to raise it. That’s a lot to carry on our backs. We’re pretty much on our own and in the best
of times the National Institutes of Health sends back four out of every five grant applications
that it receives unfunded. Now, amazingly enough we can live with that. Actually, we consider that the good times
cause right now they turned down nine out of ten or worse. In fact I have a colleague who sent an application
to one of the major charities in the United States. She got a phone call to tell her that her
grant scored number one out of one hundred sixty four applications and they weren’t sure
that they had the money to fund it. This is the only developing country in the
world that is not raising its science budgets where people who do what I do are fighting
for their very survival. There are laboratories across this country
that our closing down. Our brightest young people look at this and
ask themselves why would they want to do this and on top of this we have the shutdown. For Science, this means the National Institutes
of Health is closed. The National Science Foundation is closed. The grant giving bodies of the Department
of Defense are closed. No grants are being submitted. The review sessions to evaluate grants are
cancelled and these sessions require bringing together twenty or thirty busy people to review
these grants. So getting them going again is going to be
very difficult on top of all the human tragedies that are caused by the shutdown. So why do I do this? Well, let’s start with our cancer work. Now, let’s turn the slides on if we could. We work on a lot of horrible diseases, top
of the list is cancer and one of the cancers we work on is one of the most deadly of all,
malignant brain tumors. These are cancers that kill people usually
within six to nine months or so, progress in treating them has been very poor and we
discovered new molecular pathways that enable this work to go forward more quickly that
look really promising. But, we don’t have the time it is going to
take, the fifteen to twenty years, to develop these drugs and more importantly, the people
with these diseases don’t have the time for normal approaches. So, I’ve committed us to a different approach. Approach that I call the shot on go program
to shorten the path to the clinic and in this program what we do is we develop new applications
of known properties of existing drugs and we discover new properties of existing drugs. Why? Because we all ready know they work in humans,
the toxicology’s done, the dosing and the pharmoco kinetics are all done which means
that the number of years that it takes to get into a clinical trial is shorten enormously. The traditional approach it might take ten
or fifteen years from discovery to go to a clinical trial with a shot on go program it
may be one or two years. I’ll show you one example. That picture of survival times in mice whose
brains have been implanted with human glial blastoma cells, the most malignant of brain
tumors. We let the tumors grow for three or four weeks
and then we start treatment. The black line shows you mice that are only
treated with saline solution. The red line shows you mice that are treated
with the front line treatment for glial blastoma which doesn’t provide any benefit to these
animals plus one of the drugs that we discovered and you can see that the tumor growth is suppressed
for two weeks of treatment and when we stopped treatment instead of the tumors re-growing
,they shrank and they shrank and they continued shrinking. And the first tumors don’t come back until
a hundred days after treatment. One of the mice in this pilot experiment we
didn’t even see a tumor six months after treatment. We finally sacrificed the mouse to see what
was going on. This is a pilot experiment. This is a drug that’s already proved, even
better than that, it is a generic drug. We don’t have to negotiate with any pharmaceutical
companies. We can just go forward with this. This work is approached in a way that is unique
to Rochester. Our colleagues Hartman Land and Helene McMurray,
at the medical school, like us, have discovered pathways that nobody else works on that appear
to be essential for many many types of cancers and the pathways they work on, the pathways
that we work on both seem a minimal to these shot on goal approaches. We work with Dr. John Elfor, in the Department
of Orthopedics, on developing new ways of treating peripheral nerve injuries, traumatic
nerve injuries, gunshot wounds, crushed injuries, that again look like we’re able to greatly
hasten the time of recovery. We work on some awful genetic diseases, particularly
interested in a type of disease called lysosomal storage disorder. A lysosom is a part of your cell that’s involved
in breaking down proteins and lipids to provide nutrients for the cell. Lot of people have mutations in enzymes that
are necessary for these to work. If you only have one mutation, you’re fine. But sometimes, someone marries someone who
he has a mutation in the same enzyme and some of the kids inherit two mutated genes and
their lives can be short and miserable. Very sick at birth, death within two years. None of them have anything like the quality
of life that we would like for our children. We approach this too with the shot on go program
and I am going to show you three ten second movies. That black blob at the top is a mouse and
if you can start at movie running you’ll see that mouse running around, I hope, there he
goes and showing mouse normal behavior. In the next slide, we’re going to show you
a mouse that has one of these diseases and it is so this mouse is twenty five days old,
it has about another two weeks to live. What I want you to pay attention to is that
it doesn’t move much. It’s when it moves, it shivers, it’s weight
support is very poor. So, start the program. Start the movie. And there he is, poor, sick little guy. Not not a good quality of life, not going
to be a long life. So Christopher Falson, Nicolle Scott, two
of my graduate students, have discovered pathways, novel pathways involved in causing this damage. We have discovered drugs that prevent this
damage and this is one of our pilot experiments of a mouse treated with our first drug. So, Let’s start that one. And, this guy looks pretty good, looks pretty
normal. This is also a drug that’s already approved
for human use. In this work we’ve also discovered a lot of
bad drugs. We’ve discovered drugs that look like they
might make these diseases worse and some of these drugs are already used to treat these
kids so that’s a real concern. But, we have also opened up the door to a
problem of tremendous interest. If you carry a mutation, one mutation for
these diseases, you might think you’re normal, but we know that for example, that one of
these diseases call gashay disease, you have a six fold increased risk of developing Parkinson’s
disease. It is the strongest genetic risk factor for
Parkinson’s disease. Why? Well, what we’re testing now is the idea that
its exposure to these bad drugs. And I can tell by looking at you that there’s
quite a few of you in here who are taking some of the drugs that are on our bad hit
list just by your age distribution in the audience. It’s not just about drugs, it is also about
cells. My colleagues Margo Mar Pershell and Chris
Pershell, we discovered cells that can restore function when we transplant them in chronic
spinal cord injury that look like they may be useful in treating Parkinson’s disease. So, we’re on the cusp of changing the way
we treat horrible diseases. But given the challenges we face with federal
funding, these treatments and cures will not come quickly. People will suffer and die needlessly. So, I’d like to ask you to remember this one
equation. If you remember anything from what I said. The velocity of scientific progress equals
discovery times dollars. Well, these days we have to re-write the equation. The velocity of scientific progress equals
discovery times donations. And don’t worry, the development office has
assured me there not going to corral you today here but when they come to you help us build
a medicine by the twenty first century.

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