Space and the Hunt for a Killer App

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Ever since I read “The Man Who Sold the Moon” by Robert A . Heinlein as a kid, I have been looking for “the thing,” the “killer application,” or killer app as it is called in the computer business, that would make commercial space an economic reality.

Yes, I know all about communications satellites, but those are machines. I’m talking about people living, working and prospering in space. Having suffered many dead ends and disappointments over the years, I think I have finally found it. The Biotech Revolution, which transformed biology and medicine on Earth, must go to space.

The Silicon Valley Space Club (SVSC) is an eclectic group of people that formed to help bring the spirit of Silicon Valley to the space program. SVSC members come from the engineering and scientific ranks with a Nobel Prize winner among them, but also include high school teachers and just plain folk who are interested in space. Members of the club have been meeting regularly with the folks at NASA Ames Research Center in the heart of Silicon Valley, discussing new ways for NASA and the entrepreneurial sector to work together.

During these discussions Lynn Harper, a NASA astrobiologist who leads Integrative Studies at Ames, started explaining how the Biotech Revolution, and in particular the fallout from the human genome project, was showing startling results when combined with the microgravity of space.

The Biotech Revolution was enabled by the ability to perform high throughput analyses of DNA and proteins. These analyses provided important breakthroughs on how life works, how disease works and how we can fight disease much more effectively than ever before. Small firms jumped in where the large pharmaceutical companies feared to tread. Companies such as Genentech, Chiron and Amgen grew from small startups to industry giants in the course of a decade. The large pharmaceutical companies followed along in the trail blazed by the small, lean, innovative biotech startups.

So where does space come in?

A good cell or tissue sample can accelerate the discovery of the cause of a disease and the evaluation of potential cures by years to decades. This can save millions to billions of dollars in unproductive research and has the potential to generate billions of dollars in new pharmaceutical products while saving lives; the ultimate win-win scenario.

Researchers have found that when cells are taken out of the body and put in a Petri dish, they lose many of the important characteristics they had when they were in the body. But the value of a cell/tissue culture depends on how well the culture mimics what really happens in the body. For many diseases on Earth, there are no good cell/tissue culture models — yet. Space, or more precisely the microgravity conditions in space, appear to hold one of the essential keys to fixing this problem.

Pioneering work by astronaut David Wolf and Neil Pellis of NASA’s Johnson Space Center (JSC) in Houston demonstrated in the 1990s the potential for microgravity biotech. Microgravity enables the growth of large, three-dimensional tissue cultures that closely match the behavior of cells in the body (although we don’t exactly understand the mechanism for this). These large, three-dimensional cultures are highly desired for biotech research and have begun to prove their worth in the larger biotech community.

Over a decade ago, transplant surgeon Timothy Hammond was looking for a tissue culture model for kidney disease. Kidney disease is one of the most expensive conditions to treat because the two treatment options for advanced kidney disease — dialysis or transplant — are both very costly. The likelihood of kidney disease increases with age, and so it is rising as a national health cost as baby boomers age. With 100,000 people per year diagnosed with kidney failure in the United States, the estimated cost of treating this disease is $20 billion per year. There was no good cell/tissue culture for kidney disease until Hammond connected with Wolf, and was introduced to the JSC-developed Rotating Wall Vessel (RWV).

The RWV was invented by Wolf, Ray Schwarz and Tinh Trinh (NASA Inventors of the Year Award, 1992) to mimic the effects of microgravity on cells. Using the RWV, Hammond’s results were dramatic. Kidney tissues grown in the RWV began to reacquire their three-dimensional structure and biochemistry that had been missing in standard terrestrial cultures. Some of the biochemical products that returned to the cell were commercially important, like vitamin D3, megalin and cubilin.

Electron microscopy of the cells showed that the microvilli, an important characteristic of kidney cells in the body that had been absent in standard terrestrial cultures, returned in abundance. The team reasoned that if the RWV was good, then microgravity was the “gold standard.”

Three additional pioneering investigations in space corroborated the earlier findings in the RWV and showed even greater promise. These results were published in prestigious peer-reviewed journals and Stelsys, the entrepreneurial arm of Johnson & Johnson, became the first paying customer on the international space station as a result of both the RWV and space flight data. More work needs to be done but the results so far are very encouraging.

Even bigger news was reported this year in the journal Cell Proliferation — such a potentially huge breakthrough that it could justify all the taxpayers’ investment in space. Two British scientists working with colleagues at the University of Texas Medical Branch at Galveston have produced embryonic-like stem cells from umbilical cord blood using the RWV. The RWV enabled researchers to transform large amounts of cord-blood stem cells into liver cells.

Stem cells are potentially the most effective, life-saving weapon in the medical arsenal against disease because stem cells can turn into any cell in the body and grow as if they are part of an organ. The promise is that stem cells could repair any organ in the body — including the brain and nerves. Using the RWV, scientists successfully have formed liver tissue from the umbilical cord cells, and they’re now working to replicate pancreatic and nerve tissue. Caution is still needed in interpreting the results because the finding is still being analyzed to determine if they have all the necessary properties for therapeutic use. But preliminary results are extremely encouraging.

Using simulated microgravity could provide the incredible curative power of stem cells without the ethical issues of using aborted fetuses. And this is just the beginning.

The reason the space environment and RWV yield such improvements in cell cultures is because they more closely approximate the “cues” given to cells as they grow in the body. Cells are not smart, but they are adaptable. Give them the right cues and they behave as if they were in the body. Give them the wrong cues and their biology is different, often misleadingly different. Microgravity, and to a lesser extent the RWV, allow the three-dimensional structure of the tissues to emerge.

In space, it occurs because nutrients and wastes can be circulated via gentle mixing that better mimics the movement of fluid in the body. This allows much larger cell aggregates to form and three-dimensional structures to emerge, along with biochemical processes that more closely approximate what happens in the living body. The RWV similarly reduces shear and turbulence in the mixing process, thus providing a gentler growth environment and allowing tissues to grow in three dimensions.

The Biotech Revolution allows researchers to read the genomic instructions of how cells grow in the space environment and to correlate these instructions with their physiological meaning. Companies can then take this information and, using contemporary biotech tools, engineer the organisms and systems needed to replicate the results on Earth.

So we finally have found something that has eluded us for many years: a commercially compelling reason for humans to go to space. In the microgravity of space we can do research, the results of which can be returned to Earth and translated into products to address any number of diseases and maladies that have plagued mankind for millennia. And in the process biotech and pharmaceutical companies can make a ton of money. So where do the wheels come off this wagon?

Bringing this microgravity biotechnology potential into reality requires three things: thorough validation of the science case; timely, cost effective throughput of experiments; and education and outreach to understand and meet the needs of the biotech and the financial communities.

Validate the science

The preliminary results from the RWV and the microgravity 3-D cell culture experiments look very promising, but further validation needs to take place. Work needs to be done in space to determine which environmental cues deliver the highly desirable features of these three-dimensional cell and tissue cultures. Armed with this knowledge, researchers can optimize cell and tissue cultures on the ground. Knowledgeable researchers believe they can get another major advance via in-space research.

This research can start immediately using equipment that is already onboard the international space station. BioS erve Space Technologies (a NASA-sponsored Research Partnership Center) has a cell culture system on the international space station that makes an excellent start and can be serviced by bringing coffee can-sized research laboratories to and from Earth for rapid results.

On the ground, NASA researchers need to work with the National Institutes of Health (NIH), the Food and Drug Administration and the pharmaceutical industry to demonstrate the applicability of these 3-D cell and tissue cultures to high-priority diseases. Some of this demonstration work has started, and the NIH and other top laboratories are beginning to use the RWV as a central weapon in their attack against disease.

Throughput

Five pieces need to be put in place to achieve the necessary throughput: quick and simple experiment development and qualification; integration of experiments and supplies into pressurized cargo carriers that can dock with the space station or similar commercial facilities; frequent low-cost launches to low Earth orbit; on-orbit personnel and equipment for in situ analysis and sample processing; and frequent return of samples to Earth.

These solutions do not require the space shuttle, but do require investment to provide the critical new capabilities on-orbit that enable throughput.

There are any number of commercial companies that are willing and in some cases able or getting close to providing the necessary services (other than the Russians) such as Spacehab, Constellation Services, Space Exploration Technologies (SpaceX), Bigelow, BioServe and t/Space to name only a few. The NASA Ames Research Center is even offering to be the “friendly front door” to assist potential users in maneuvering through the bureaucratic maze.

Other NASA centers, including Johnson and Marshall Space Flight Center in Huntsville, Ala., also are attempting to reach out to the commercial community.

These companies are willing, as NASA Administrator Mike Griffin so eloquently put it, “to put some skin in the game.” In this case, the skin is private money that the companies already have invested to move their designs and build flight hardware. What they need from NASA is a reliable customer.

Outreach

The really big unknown in this equation is NASA. The requirements for flying an experiment on the space station today are daunting to say the least. The time to flight is measured in years and the forms that need to be filled out make applying for a home loan seem trivial. Reflights, when they happen, often takes years. When the idea of a customer-centric space station was presented to Griffin, he commented that he never expected to hear those words used in the same sentence.

Can the international space station system transform to the point where commercial companies are willing and able to work with NASA (and whatever other organizations may be set up to assist in this effort) to perform biotech experiments on the space station?

I am cautiously optimistic. It is comforting to know that Bob Bigelow is launching the first one-third-scale model of his expandable modules next February and expects to have a full-scale module on orbit by 2010 ready, willing and eager to accommodate paying commercial customers. The biotech and financial communities need to see a clear, stable and profitable path to space research before they will be willing to invest.

But, just as we stand on the verge of being able to fulfill the promise that NASA made to the American people over 20 years ago about the utility of the international space station, NASA has decimated the research budget necessary to carry this out. I am not saying that there were not some cuts that could and should be made in the NASA life sciences program, but to eliminate entire programs without appropriate review may be tragically short-sighted.

Recommendations

– Do not stop space life sciences research. The findings so far are astonishing and yet only a glimpse of the full potential.

– Encourage the development of private space infrastructure to provide routine, low-cost access to space, available on-orbit research facilities and frequent return of samples from space.

– Continue research necessary to prove the science case for biotech research in microgravity. Coordinate with other agencies such as the NIH. Spread the results outside the normal space research community into the wider biotech community.

– Provide a single, senior-level manager (with appropriate budget) responsible for making NASA a reliable, user-friendly partner in microgravity research. This will require significant streamlining and culture change. If NASA cannot do this alone then I am sure entrepreneurs such as Bob Bigelow would be happy to step in and help.

– Provide the “friendly front door” to commercial space research and reach out to the biotech industry to show them the promise space offers and let them know that the government really is here to help with flexible and innovative programs.

We have made a huge investment in space infrastructure over the last 30 years. The shuttle did not live up to its promises. Let’s make sure the international space station and the microgravity research it can support also does not fall short. What we are talking about here is more important than the space program. It has the potential to positively affect the quality of life of everyone on Earth.

Bruce Pittman is a consultant, space entrepreneur, president of the Silicon Valley Space Club and a founding member of the Alliance for Commercial Enterprises in Space (ACES).