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3-D Tissue Engineering for Selection of Chemotherapies

This case study was conducted in FY 2013 by the Emerging Space Office (ESO) to begin characterizing the kinds of opportunities and challenges encountered by small high-tech businesses who have never done R&D in space and who serve terrestrial versus space markets, but who have legitimate business reasons for considering space research and development for generating novel or improved products. 

The primary motivation for ESO’s interest in this investigation was to gain insight, through direct support of an emerging commercial space project as a case study, into the conditions important for the successful maturation of the International Space Station (ISS) into a multi-faceted, multi-user National Laboratory for providing social and economic benefits to the U.S. The ISS is the core of the human spaceflight economic ecosystem in orbit and is the primary test-bed for investigating and understanding how to productively work and live in space.

Other than providing funding for the $50K grant, NASA was not involved in any part of this study except as an observer.  The entire effort was conducted by Vivo Biosciences Inc. (the small business customer) and BioServe Space Technologies (the space services provider).  This case study is for information only and should not be considered an endorsement of either the company or its products.



Case Study Report:  Vivo Biosciences Inc.  –  The Customer’s Perspective
Executive Summary



Why Does a Biotech Company Want to do Research in Space?

Vivo Biosciences Inc. (VBI) is an award winning company with a customer base that includes major pharmaceutical companies.

Their unique product (HuBiogel™) and 3-D tissue and tumor culture system was named by The Scientist Magazine as one of the Top Ten Innovations of 2012.   HuBiogel™ is used in the Rotary Cell Culture System, which is a NASA spinoff now produced and marketed by Synthecon, that has some of the low shear and turbulence features of microgravity that are important in 3D tissue cultures.  VBI’s HuBiogel™ system is used to grow tissues and tumors for cancer research and is now also a leading new candidate for use in the selection of chemotherapy drugs for cancer patients.

However, despite a continuing series of successes, VBI believes that they are about at the limit of the performance their product can achieve on Earth and gravity is the problem. 

To develop better life-saving therapeutic options, VBI needs 3-D tissues and tumors that are both bigger than what they can achieve on Earth and of higher fidelity to disease processes in a patient.  Reluctantly, VBI concluded that space might be the best place, and perhaps the only place, to get the improvements in performance they need.

VBI does not know whether growing tumors in space will improve their product’s performance. But if it does, the results would be important to many research areas, including selecting the right chemo-therapy options for patients.  This is potentially life-saving research that could offer significant near-term benefits to the public.
Purpose of Case Study

Vivo Biosciences Inc. (VBI) submitted an unsolicited proposal to the Emerging Space Office (ESO) in 2012 and was selected for a case study in FY 2013.  From ESO’s perspective, the purpose of this study was to understand the kinds of options, motivations and difficulties encountered by small high tech companies that have legitimate business reasons for using space to improve existing products or develop new ones for a terrestrial market; especially those with no prior space experience.

VBI needed to know if they could grow tumor cells on HuBiogel™ in existing flight hardware well enough to make a flight investigation worth the effort and expense and obtain answers within the next three to five years. 

Opportunities for Public Benefits


In 2013, while this Case Study was underway, VBI con-ducted a landmark study with Champion Oncology to address the selection of chemotherapies for two types of cancer: a drug sensitive colon cancer and a drug resistant colon cancer.
 
Champions Oncology provides diagnostic support to physicians in the selection of chemotherapies.  They take cancers cells directly from a patient, grow that patient's tumor in a mouse, then test a variety of dif-ferent chemotherapeutic agents to see which drugs work on that patient's specific type of cancer. 

The problem is that it takes 20-30 weeks to grow the tumors in the mouse and Champions Oncology was seeing too much variability in the results.

In addition, colon cancer is a very aggressive cancer.  Thirty weeks can be too long to wait before starting cancer therapy.  This is where Vivo Biosciences offers a potentially significant improvement.
  

Chemotherapeutic agents are poisons that significantly weaken the patient. 

They are used because cancer cells are often weaker than healthy cells to certain chemicals and the goal is to eradicate the cancer before killing the patient. 

Treating a patient with the wrong chemotherapeutic agent not only will not work to destroy the cancer cells, it will also further weaken an already seriously ill person. 
 
In a blind study using VBI’s technology, patient tumors provided by Champions Oncology were grown in HuBiogel™ at VBI and treated with known drugs along with control samples. 

In the very first study performed, HuBiogel™ tests were correct in 70-80% of the cases, but it only took 2-3 weeks to get the results and not 30 weeks.
 
This speed can make a critical difference for a patient suffering from colon cancer and other aggressive cancers. 
 
The goal now is to predict and achieve >90% accuracy in 2 week analyses.  Achieving this accuracy is where VBI believes that space research could make the difference.


The High Cost of Learning


VBI was highly motivated to make the flight hardware evaluation test work. 

The insights gained from their successes and prob-lems are useful for understanding where NASA and CASIS can play critical roles in achieving better out-comes for public benefits from both the ISS and the emerging commercial space transportation and services companies.

$50K was provided via an ESO grant to VBI to deter-mine whether they could grow tumors in existing flight hardware. 
Of the  $50K ESO funding:
$28K supported the Vivo Biosciences Principal Investigator and a part time temporary research assistant for preparation and analyses of samples;
$11K went to BioServe Space Technologies for leasing the flight test unit (BioCell) and design services; and
$11K went for tissue culture supplies and reagents used to grow and analyze the samples. 

The test required successfully managing the culture conditions and fixation strategies for 4-6 weeks in the flight hardware under anticipated space flight conditions. 

Then VBI evaluated the adequacy of tumor growth and function in the BioCell using imaging and bio-chemical analyses.

The results determined whether a flight investigation had a high probability of yielding new important insights for project improvement.
 
After six months, Vivo Biosciences concluded that some but not all of their technical goals could be met because the culture chamber was too small. 
 
However, they did determine that there were no fundamental biocompatibility issues with the BioCell materials and that they could manage the tissue growth environment for the necessary 4-6 weeks. 

With a minor redesign of the flight hardware, this experiment could be conducted in space within a year … if funds were available to support it.  
 
Which as of this writing, there are not.


Pitfalls and Pathfinders


Nobody does biotech research on earth the way it must be done in space.  The procedures are not even close.  Terrestrial labs do not have to manage launch stresses, unwanted and non-intuitive effects of microgravity, re-entry stresses, and post-flight recovery delays.  
In fact, laboratory research in microgravity is so different from anything a typical laboratory scientist would expe-rience on Earth that it is akin to pursuing a graduate degree in a new technical subject. 
Novice investigators need considerable help to suc-ceed, especially if flight research is only a minor part of their business model. 

Like Vivo Biosciences, commercial biotech research will seek specific research outcomes that are likely to require changes in flight hardware. 
Few companies, even large companies, can afford to spend $50K and six months of their own resources to determine that the flight hardware is not adequate for their investigation; wait six months or more for a re-design; then spend an additional $50K (or more) to test the new hardware again before committing to a flight (costing in excess of $200K)  that may or may not yield a productive outcome.  For large companies, this is unattractive.  For small companies, it is prohibitive.

However, these small companies are often the pathfinders for new capabilities in high tech industries and they offer the innovative culture that can pioneer important new uses for the ISS National Laboratory, serving both the nation and NASA’s interest well.


The Vivo Biosciences flight concept:
Addresses an important public need (cancer research and applications),
Serves a terrestrial rather than flight market,
Requires space to achieve it’s goals (currently, accuracy is limited by tumor size and characteristics which are limited by gravity),
If successful, this study could result in an important breakthrough.  But success is by no means assured.

This is an exploratory commercial applications proposal  for a terrestrial market, rather than space biology basic research, space technology development, or space biomedical research.

Although Vivo Biosciences is a small business, VBI does not address a space market and so is not eligible for NASA’s SBIR/STTR funding.  

As such, this proposal falls through the cracks of NASA’s R&D portfolio and the high risk nature of the space element makes it unattractive to most private investors.

Parts That Work


Flight accommodations as currently configured are not customer-friendly for novices, although BioServe Space Technologies provided excellent support to Vivo Biosciences throughout the study.
 
In fact, the role of a mentor or guide (like BioServe) who provides a bridge between the needs of a novice flight investigator and the accommodations and constraints of space flight is the single most essential element in crafting a successful research experience for new entrants into space laboratories.
Case Study Report:  Vivo Biosciences Inc.  –  The Customer’s Perspective
Executive Summary
From VBI’s commercial perspective, that the International Space Station (ISS) is immediately and permanently available for iterative research, and that SpaceX Dragon can provide the critical return of samples to earth as well as payload transportation to the ISS, were all essential to VBI even considering trying to improve their product in space.  In this case, sample return is a deal-maker.


Conclusion:

 
For any company, time is money. 
 
During the six months that Vivo Biosciences conducted the ESO Case Study, it also completed two landmark studies for paying customers, which illustrates another point. 
 
The priority of companies, especially small companies, must be to support their paying customers while the space flight investigations are being developed.  Often they won’t have the resources to do both with internal funds.
 
The amount of time it takes to do a space flight investigation (years) is significantly out of scale with a commercial laboratory investigation on Earth (days to weeks). 
 
Vivo Biosciences believes that removing gravity to obtain larger, better-quality tumors is one of the few, and perhaps the best, option it has for improving research and cancer treatment outcomes with their product.

But it still might not work and they can’t afford to fund the wrong strategy. 

Unfortunately, three outcomes are possible with this investigation and, from a company’s perspective as a potential paying customer,  two of them are bad.


First, the experiment might not work at all, either because microgravity doesn’t help achieve the desired results or because of mechanical problems, operational issues or simply bad experiment design resulting from inexperience with space flight realities.

Alternatively, there may be some improvements from space but either they are not significant enough or their value is diminished by other negative effects of growth in microgravity and the outcome turns out not to be worth the cost.
 
Third and best, the space flight results are what the commercial researcher hoped to achieve.  In which case, the company will need to fly the experiment again to confirm it and then many more times to develop sufficient reliability and confidence for a marketable product.  This is a very expensive, likely prohibitively expensive, undertaking for a small company.
 
Unfortunately, there is no way to develop, or even to determine, the value of removing gravity for advancing this type of potentially life saving research without doing the experiments in space.

Recommendations:


Nationally, there are insufficient funds for early stage exploratory applications research, like VBI’s, that investigates unproven but promising microgravity techniques and addresses a terrestrial versus space market.
 
In fact, if the government does not help this new field of laboratory sciences to grow, it is unlikely to develop the critical mass of talent and ideas necessary to achieve the number and kinds of breakthroughs that can offer important new outcomes for the taxpayers’ investments.  Alone, CASIS’ funding is insufficient to realize the potential this type of research offers.

Case Study Report:  Vivo Biosciences Inc.  –  The Customer’s Perspective
Executive Summary
The ISS and commercial space synergy are capable of delivering even more value to the public than the many contributions they have already achieved.

Therefore, it is strongly recommended that NASA establish funded solicitation mechanisms to encou-rage worthy applications R&D in space, at least through the initial flight test, when such studies have the potential to yield important public benefits, even if they don’t provide a NASA application or fit within standard programmatic boundaries.

Mentors, advisors, guides and integrators (MAGIs) who can help a novice craft a successful flight experiment –  like those at Bioserve Space Technologies, Dr. Lawrence DeLucas at University of Alabama, Nanoracks, and investigator flight support groups at NASA Centers – are essential to the development of the ISS National Laboratory and the commercial microgravity laboratory market that could become important to emerging space companies. 

Because they play such essential roles in delivering value back to the public from spaceflight, it is recom-mended that the MAGIs be supported to maintain critical staff expertise during the intervals between funded flight developments.

Novel research of the kind that can lead to breakthroughs will almost always require hardware modification.

Some mods will be relatively easy and cheap, like those required by Vivo Biosciences.

But some that are important for opening new markets – like onboard analyses and the ability to handle sensitive biological samples on the launchpad, through the launch interval,  and during return to Earth – may need funding in the $5M-$10M category.
However, given the magnitude of taxpayer invest-ments to build the ISS and the billions of dollars per year spent in operating it, increasing funding to sup-port more space research for public benefit and in-creasing the investment in infrastructure that makes more breakthroughs possible is a sound and worthy strategy, even with the challenges of sequestration.

The Vivo Biosciences flight concept is worth doing.  It will offer valuable information to NASA and the emerging space community on the challenges facing new commercial entrants into the field of space research – whether VBI succeeds in meeting its research objectives or not. 

Therefore, it is strongly recommended that both NASA and/or CASIS continue to support VBI’s investigation through flight and that ESO monitor its progress because of its:
Potential benefit to public health;
Utility as a Case Study for this class of commer-cial biotech research in space for a terrestrial (rather than space) market; and
Value in understanding the customer perspective and developing the commercial research and applications potential of the ISS and the commercial space transportation and service providers that are evolving with the ISS National Laboratory.

Finally, it is strongly recommended that NASA and CASIS continue their wise practice of encouraging and supporting exceptions to standard plans and procurement strategies for flight studies when “out of the box” and “out of the blue” proposals offer the potential for exceptional outcomes that could serve the public in important ways.






http://www.southernresearch.org/news/2010-04-16-southern-research-and-vivo-biosciences-announce-collaborative-co-marketing-agreement

http://www.the-scientist.com/?articles.view/articleNo/33341/title/Top-10-Innovations-2012/


http://www.businesswire.com/news/home/20101006005776/en/Vivo-Biosciences-ACEA-Biosciences-Roche-Develop-xCELLigence#.VQ3_YUYkMUE


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Lynn Harper,
Mar 21, 2015, 4:27 PM
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Lynn Harper,
Mar 21, 2015, 4:28 PM
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