Timothy Hammond
Langdon
We're going to start again. The presentations will be more brief. Remember
to turn off your cell phones during the session. With that let's carry
on.
Lynn
The human genome project was a revolution in biology. My husband and I
thought "if only we could apply this to space." Then, Emily
Holton who was a catalyst in so much of this brought me a letter from
Dr. Timothy Hammond. Dr. Hammond has done a lot of research on genes and
how their expressions have changed due to space flight. There's a huge
potential for discovery and advances that are medically important.
The value of a cell culture model for pharmaceutical development is how a cell can better mimic what happens in the human body. Tim is one of the pioneers in the field so he's going to make a presentation on the past and present work that's been done. He received his medical degree from the University of Melbourne. He has worked at Harvard and many other places. Now I want to introduce Tim Hammond.
Timothy Hammond
I want to start with a story. If you ever go to Amsterdam you must visit
the city of Haarlem which is outside the city. It is one of the birthplaces
of modern biology. There is a museum there that commemorates some of the
most historic achievements in biolgy. There are two huge statues of a
man and woman outside of the museum which have stood for centuries. There's
a story that the statues at the museum asked to become mortal for half
and hour according to legend. Their wish was granted and they became mortal
for just 30 minutes. The male statue turned to the female and said that
they should make the most of their 30 minutes, so he winked at her and
they went behind the museum. They went behind the museum and all you could
hear were the sounds of joy and ecstasy. After the half hour they were
going to get turned back into statues but the female statue pleaded for
more time because she said that while the male was satisfied she didn't
have enough time to get her satisfaction. So they were granted ten more
minutes of mortality. The male said, "okay, but this time I will
hold the pigeon and you poop on it." So the theme of today is things
are not always what they seem.
So we came to the realization that we didn't have the tools we needed for the clinical bedside needs. The point of this slide is that the kidney cells in mono cultures do not replicate the human body like they should. Our challenge was to reproduce the cells better. Cublin and megalin were what we studied. These two proteins are lost in the mono cultures, but we needed to optimize them. We met David Wolf and collaborated. That led us to the optimization of suspension culture. Renal dialysis is a multi billion dollar industry that we can capitalize on if we meet the opportunities available. Our commercial partners wanted to produce hormones. We need to understand cublin and megalin.
The RWV is our ground-based model. The red is megalin and the blue is cublin. There are islands of megalin and cublin in a fairly normal study. In the RWV we were able to increase vitamin D3 in these 3-D cultures and this is very important.
Equation
We needed a simple equation on how gravity affects what's going on. The
velocity and the sheer of the fall is affected by gravity. So we came
up with this equation. The problem is that this equation assumes that
density and viscosity are independent parameters, but they are not and
you can never study them independently. So you have to get rid of gravity
completely and do the research in space to actually model what happens
in reality.
The rotation speed is not related to sheer. Rotated speed does determine the size of the cell spirals if you spin at different speeds. It's a cork screw effect. The problem on the ground is that you cannot separate the various elements so we wanted to understand how the cells work in space.
So we wanted to see if we could turn off the vitamin D receptor. So here's a picture of David Wolf in space working on the project. We flew the cells in space and fixed them in space and when they came back we extracted RNA. Then we examined the results on an array -- we had 10K genes in the array. The STS-90 genomics results were very surprising. Over 800 genes changed in the RWV but more than double that changed in flight. The two that changed the most was a gene that mediates cancer in children and the vitamin D receptor.
So we had to do more research. Lynn told us to write the
right application and that we could do it for $5M over five years. But
we didn't have that kind of time or money so we leveraged our educational
position. The second thing we did was to find a commercial partner. Then
we put together a $300K package to do a reflight within one year. Cellsus
was the corporate company that came to us to help fund the project. We
were able to keep the cells for 10 days. The automated hardware was made
by Lou.
The automated hardware has flown many times, it needs a lot of power though. The automated hardware is much more practical. By the time we did the second round of experiments we had increased our knowledge by an order of magnitude. We had good vibrations, centrifuge, and ground controls and that helped us do a good experiment.
So we came to two conclusions. First, vitamin D is fairly simple to reproduce in the RWV. To our great surprise the Urokinase does extremely well in the three dimensionality of the beads tests. The other thing was that the Urokinase inhibits its own production in the vessel. We want to see if we can make a much larger production.
In-flight there are five isoforms of this protein group. The next surprise was the Cytochrom P450 group. They are liver cells. We found dramatic expression of the cells in flight.
This is another example of florescence from the STS-105 study.
Our partners were interested in renals but also in hepatocytes. The government was also very interested in this and the FDA for the first time mandated a study of the hepatocytes. Our partners wanted to know if they could use the RWV and space flight to do their studies. They showed that they could keep the normal cells alive longer in RWV and flight. So the cells flew and we got enzyme changes that we could measure but if we could do it over we would do many things differently. If we are going to fly experiments in space we should do a small model flight first to shake out the bugs.
Spaceflight can be used to optimize commercial products like liver cells for drugs. These people helped put this work together.
Questions
How far along is this work in terms of turning into a commercial product?
The Urokinase is protected. One of the questions is working out all the other intellectural property issues. In the liver cells there's a lot of interest in growth metabolism and there's intereste in creating an artificial liver. In terms of renal hormones there's also interest. Nowadays we are using mixtures of 125 and 424 or some other thing to make vitamin D. As you can see, the market doesn't stand still..
I work for the VA and our method of delivering care can be too entrenched. My message is that diversity is healthy and can lead to new discoveries -- I welcome the commercial side becoming involved in this.
Are there derivatives of the hardware that can be flown without humans and are fully automated?
There are a number of providers of automated hardware. All they require are status checks. There are many creative ways to do studies. There are a lot of different hardware available, but the technology is very complex and all of them have had some level of problem in the past.
You engaged students and commercial partners together can you apply that beyond the small initial application?
There are others that can answer that better than me, but I think the bottom line is "yes." There are issues of timing with science and commercial properties that are important.
There's the question of, "if this is so great why aren't more people doing it?" Is it just a case of people not knowing or being prejudiced against NASA?
I think that it is not simple to bring a commercial partner willing to spend six figures, a flight opportunity, and academia together. The challenge now is that NASA is influx. You have to show the parties that what you're doing is really worthwhile.