Team:Stanford-Brown/Integrated Practices
Integrated Human Practices
We have organized the “human practices” elements of our research this summer into two categories, which follow from the two spaces in which our technology might be applied: outer space and Earth.
Space Applications: Planetary Protection
We were initially inspired to create a bioballoon for atmospheric research on Mars and other planetary bodies. Planetary scientists need to find ways to feasibly investigate the life history of other planets while still preserving these spaces as pristine environments for future generations of researchers. We wanted to develop a tool that could help them.
We spoke to several planetary scientists about the profound significance of responsible research on planets like Mars and Venus and on moons like Titan and Europa. These researchers included Dr. James Head, Louis and Elizabeth Scherck Distinguished Professor of Geological Sciences at Brown University, investigator on several NASA and Russian Space missions, and current co-investigator for the NASA MESSENGER mission to Mercury and Lunar Reconnaissance Orbiter; Dr. Lynn J. Rothschild, our team PI, evolutionary biologist and astrobiologist at NASA Ames Research Center, Adjunct Professor at Brown University (Molecular and Cellular Biology and Biochemistry) and at UC Santa Cruz (Microbiology and Environmental Toxicology); Dr. Jill Tarter, Bernard M. Oliver Chair for Search for Extraterrestrial Intelligence (SETI) Research at the SETI Institute in Mountain View, California; and Dr. Alan Stern, former chief of all space and Earth science programs (2007-2008), current leader of NASA’s New Horizons mission to Pluto and the Kuiper Belt, and current Chief Scientist at World View Enterprises, a company developing high-altitude balloons for commercial use in research and private space exploration.
(Listen to the podcasts of our interviews with Dr. Rothschild, Professor Head and Dr. Tarter here.)
We spoke to several planetary scientists about the profound significance of responsible research on planets like Mars and Venus and on moons like Titan and Europa. These researchers included Dr. James Head, Louis and Elizabeth Scherck Distinguished Professor of Geological Sciences at Brown University, investigator on several NASA and Russian Space missions, and current co-investigator for the NASA MESSENGER mission to Mercury and Lunar Reconnaissance Orbiter; Dr. Lynn J. Rothschild, our team PI, evolutionary biologist and astrobiologist at NASA Ames Research Center, Adjunct Professor at Brown University (Molecular and Cellular Biology and Biochemistry) and at UC Santa Cruz (Microbiology and Environmental Toxicology); Dr. Jill Tarter, Bernard M. Oliver Chair for Search for Extraterrestrial Intelligence (SETI) Research at the SETI Institute in Mountain View, California; and Dr. Alan Stern, former chief of all space and Earth science programs (2007-2008), current leader of NASA’s New Horizons mission to Pluto and the Kuiper Belt, and current Chief Scientist at World View Enterprises, a company developing high-altitude balloons for commercial use in research and private space exploration.
(Listen to the podcasts of our interviews with Dr. Rothschild, Professor Head and Dr. Tarter here.)
These researchers conveyed to us the inestimable value of origin of life research on other planets. This research helps us better understand and appreciate our position in the universe. It forces us to reconsider our definitions of life (if we found “life” on another planet, would we recognize it?) and confront the precariousness of human existence (what were the conditions that allowed life to appear and evolve on Earth?). NASA research on Mars also explores the possibility of human interplanetary colonization.
Interplanetary research is expensive both in terms of money and of time. It depends upon sturdy, efficient research tools that can supply information to current scientists without compromising future studies. Biological research tools (like our balloon) that could be developed onsite and thus eliminate transportation costs would, in theory, propel research forward. However, any potential benefit to this technology would be quickly negated if those tools were to contaminate the planet with Earth life.
Developers of biotechnology for space research therefore need to go to great lengths to mitigate the risk of interplanetary contamination. NASA’s Office of Planetary Protectionhas established a set of guidelines by which to evaluate appropriate precautions for planetary research.1 These guidelines are designed to protect “solar system bodies […] from contamination by Earth life, and [to protect] Earth from possible life forms that may be returned from other solar system bodies.” The policies most relevant to our summer research include “NPR 8020.12D: Planetary Protection Provisions for Robotic Extraterrestrial Missions” and “NPG 8020.7G: Biological Control for Outbound and Inbound Planetary Spacecraft.” Since our bioballoon would ideally be used for research on planets with the potential to support Earth life, it would need to comply with the Mission Category IVb and IVc regulations designed for landing/probe missions investigating extant life on Mars.
After reviewing these documents, we quickly realized that if we wanted to develop a practical tool for interplanetary life research, that tool would need to be completely devoid of life. Though our materials could be produced in living organisms, the final balloon mechanisms would need to work in vitro. We then determined our project categories:
Interplanetary research is expensive both in terms of money and of time. It depends upon sturdy, efficient research tools that can supply information to current scientists without compromising future studies. Biological research tools (like our balloon) that could be developed onsite and thus eliminate transportation costs would, in theory, propel research forward. However, any potential benefit to this technology would be quickly negated if those tools were to contaminate the planet with Earth life.
Developers of biotechnology for space research therefore need to go to great lengths to mitigate the risk of interplanetary contamination. NASA’s Office of Planetary Protectionhas established a set of guidelines by which to evaluate appropriate precautions for planetary research.1 These guidelines are designed to protect “solar system bodies […] from contamination by Earth life, and [to protect] Earth from possible life forms that may be returned from other solar system bodies.” The policies most relevant to our summer research include “NPR 8020.12D: Planetary Protection Provisions for Robotic Extraterrestrial Missions” and “NPG 8020.7G: Biological Control for Outbound and Inbound Planetary Spacecraft.” Since our bioballoon would ideally be used for research on planets with the potential to support Earth life, it would need to comply with the Mission Category IVb and IVc regulations designed for landing/probe missions investigating extant life on Mars.
After reviewing these documents, we quickly realized that if we wanted to develop a practical tool for interplanetary life research, that tool would need to be completely devoid of life. Though our materials could be produced in living organisms, the final balloon mechanisms would need to work in vitro. We then determined our project categories:
- We would need to produce materials in bacteria that could be used for a balloon membrane. These materials would need to be thoroughly purified and separated from live cells before balloon construction.
- We would need to come up with atmospheric sensing and UV protection mechanisms that could operate in vitro and attach to a balloon membrane.
The problem of how one might operate a Mars onsite synthetic biology lab and sterilize the resulting materials remains an area for future research. However, we have intentionally designed our bioballoon so that it might be compatible with future protocols.
Earth Applications: The Problem of Environmental Sustainability
Biologically produced materials and sensors have important applications closer to home as well. Latex, for example, is used in a variety of commercial products (including balloons). We decided to use our latex project example to frame questions about the feasibility and potential benefit of our work for Earth manufacturing.
We found ourselves asking, “What would be the real benefit of being able to produce latex in bacteria for Earth applications? We tend to assume that we’re working on an environmentally friendly technology, but would our method really be more environmentally friendly than growing latex in Southeast Asia?” We started reaching out to people who might be able to help us answer these questions.
First, we met with Dr. Anne Schauer-Gimenez of Mango Materials, whose company produces polyhydroxybutyrate (PHB), a biodegradable plastic, by a novel method. Like other biomaterials companies, Mango Materials depends on bacteria to produce their plastic; however, their bacterial ecosystem runs on methane gas. In theory, the Mango Materials plastic should create a closed-loop cycle: methane fuels plastic production, the plastic releases methane upon degeneration, and the same net methane is used to produce more plastic. The Mango Materials PHB would replace polypropylene, which is made from fossil fuels.
When I (Amy) met with Dr. Schauer-Gimenez, she explained that her company was in the midst of the difficult scale-up process. There are many stages to this process: biomaterials manufacturers must adapt their procedures to increasing scales of production, and there are many decisions to be made along the way. Take one example: Dr. Schauer-Gimenez mentioned that the USDA facility, where Mango Materials does pilot testing, houses eight different industrial-scale centrifuges. Mango’s original protocols were developed in Stanford research labs, where the team used typical lab bench centrifuges. They now need to predict which industrial-scale centrifuges best suit their purpose. The Mango team has run into many such unanticipated junctures while transforming their lab success into a commercial-scale process, and they have had to “wing it” a bit. Dr. Schauer-Gimenez laughed while telling me about one Macgyver-like strategy to filter wastewater for feedstock: the team lined up Costco water filters, connecting them with pipes from Home Depot. The next scale-up level would require an entirely different strategy by which to accomplish this step. Dr. Schauer-Gimenez told me that the greatest unanticipated expense for fledgling biomaterials companies tends to be spent figuring out how to extract desired polymers from cells. Typical lab techniques (like using chloroform to dissolve cell membranes) are not scalable. Companies like Mango Materials develop their own secret protocols to address this problem.
The Mango Materials PHB will need to be price competitive with polyactic acid (PLA) and polypropylene in order to achieve goal impact, Dr. Schauer-Gimenez explained, because 80% of consumers care only about cost efficiency. PLA currently sells for around $1 per pound, while polyhydroxyalkanoates (PHA), the larger category of biodegradable plastic which includes PHB, sells for about $3 per pound. Dr. Schauer-Gimenez laughed: “Even our Berkeley friends who are environmentally conscious won’t pay $3 a pound for plastic!”
By the time our meeting was over, I had realized that investment in scale-up was not trivial. Without going through this process ourselves, it would be difficult to realistically project price, yield, and environmental impact of our latex manufacturing method. This meeting also reinforced the message to our team that we will not be able to influence manufacturing practices unless we can sustainably sell latex at or below prevailing market prices.
We next met with Murthy Konda and Binod Neupane of the Joint Bioenergy Institute (JBEI) Techno-economic Analysis Team to get advice about how to predict and assess the feasibility and sustainability of our latex production. Dr. Konda and Dr. Neupane reaffirmed the difficulty of projecting yields, price points and environmental impact when beginning an unpredictable scale-up process. They explained their strategy: the techno-economic analysis team sets a price point (or carbon emission) goal for an overall process, and then they develop a computational model to establish the thresholds that individual project teams must meet to achieve that goal. They encouraged us to set goals based on maximum lab yields and standard industrial operations costs and adjust from there.
Taking Dr. Konda and Dr. Neupane’s advice, we decided to develop a vision of our end goal: if we were going to compete with natural latex, priced at less than $1 per gallon, then we would surely need to operate on a massive industrial scale. We set up a meeting with Jeff Davis, Head of Operations and Engineering for US Biologics Process Development at Genentech. I (Amy) asked him if he could help me predict, based on gross assumptions about the scale-up process, what we would need to run an industrial-scale latex bio-manufacturing facility and what price we might expect to set for our latex. He told me that a facility supporting 2,000L fermenters would likely cost around $200 million, while a facility supporting 25,000L fermenters would cost around $1 billion. He helped me develop a back-of-the-envelope estimate: a 25,000L bioreactor facility operating at full capacity could probably produce our polymer at close to $2-5 per gram. This would be far outside our goal price of $1 per gallon. (This estimate was, of course, based on experience with pharmaceutical production, which involves a more complicated series of testing and purification steps. Even so, we took this into account to produce a more generous estimate.)
Even at this massive scale, it is unclear that our latex production would be environmentally friendly as compared to traditional farming. Genentech uses a huge amount of water: judging by their 2015 corporate sustainability letter, their water usage is equivalent to that for roughly 10% of households in San Francisco County.23 Of course, Genentech has a massive facility that produces large amounts of pharmaceuticals, and based on my conversation with Mr. Davis, the same processes that ensure the purity (and safety) of pharmaceuticals seem to be some of the most water-intensive. (One can tell, too, from the corporate sustainability letter, that Genentech takes water usage goals seriously.) However, in the case of materials manufacturing, for which environmental sustainability would be an intended selling point, this level of water consumption might not be justifiable.
Finally, we met with Michael Lepech, Assistant Professor of Civil and Environmental Engineering at Stanford University, who has expertise in life cycle analysis (LCA) and has conducted research with NASA on the use of biomaterials for construction. Professor Lepech left us with two key takeaways. First, he emphasized that the environmental impact of a process is inextricably linked its energy source. Any bio-manufacturing facility in the US is mostly running on fossil fuels. Only about 13% of US electricity comes from renewable energy sources.4 Second, the production and distribution channels for traditional manufacturing materials have become so efficient that it is nearly impossible for biomaterials to compete on price alone. (I pointed out that localized manufacturing of latex might cut down on environmental and monetary transportation costs. In response, Professor Lepech pointed at my shirt: “Only about a dime was probably spent on transport for that.”) Because bio-manufacturing is so expensive and yields are so low, the market currently incentivizes bio-manufacturing of small, expensive products. Pharmaceuticals are the perfect fit, as are expensive, complicated materials (like Bolt Threads’ spider silk5).
What does the future look like for other biomaterials? Professor Lepech gestured to his work with NASA as a way forward. On a place like Mars, there is no market competition. Astronauts have only limited resources, and bio-manufacturing methods might make most efficient use of limited resources. It could be, then, that space exploration will provide the necessary incentives to develop biomaterials, incentives that our Earth market economy lacks. Once developed for space, Professor Lepech suggested, these materials might make their way back to Earth. Professor Lepech, whom we met through Stanford connections, had surprisingly led us back to NASA.
Our team ultimately integrated our research into the design of our project by reinvesting in the idea of developing space materials that might be repurposed in years to come. We came to appreciate the greater role that NASA plays in propelling research that might not otherwise happen. And in our meetings with the Stanford Space Initiative and with Dr. Alan Stern of World View, we attempted to better understand existing needs in space exploration that might be met by biomaterials.
(A side note: We also met with Dr. Stephen Comello, Associate Director of the Sustainable Energy Initiative at Stanford Graduate School of Business, who encouraged us to reach out to major rubber manufacturing companies and ask them how our technology might impact their operations and marketing strategies. We contacted Michelin Tires to ask them about their new sustainable natural rubber policy.6 We saw this policy as indication that tire companies might be looking for more sustainable sources of rubber, since natural rubber plantations currently contribute to deforestation and are susceptible to blight.7 However, we have yet to hear back from Michelin.)
When I (Amy) met with Dr. Schauer-Gimenez, she explained that her company was in the midst of the difficult scale-up process. There are many stages to this process: biomaterials manufacturers must adapt their procedures to increasing scales of production, and there are many decisions to be made along the way. Take one example: Dr. Schauer-Gimenez mentioned that the USDA facility, where Mango Materials does pilot testing, houses eight different industrial-scale centrifuges. Mango’s original protocols were developed in Stanford research labs, where the team used typical lab bench centrifuges. They now need to predict which industrial-scale centrifuges best suit their purpose. The Mango team has run into many such unanticipated junctures while transforming their lab success into a commercial-scale process, and they have had to “wing it” a bit. Dr. Schauer-Gimenez laughed while telling me about one Macgyver-like strategy to filter wastewater for feedstock: the team lined up Costco water filters, connecting them with pipes from Home Depot. The next scale-up level would require an entirely different strategy by which to accomplish this step. Dr. Schauer-Gimenez told me that the greatest unanticipated expense for fledgling biomaterials companies tends to be spent figuring out how to extract desired polymers from cells. Typical lab techniques (like using chloroform to dissolve cell membranes) are not scalable. Companies like Mango Materials develop their own secret protocols to address this problem.
The Mango Materials PHB will need to be price competitive with polyactic acid (PLA) and polypropylene in order to achieve goal impact, Dr. Schauer-Gimenez explained, because 80% of consumers care only about cost efficiency. PLA currently sells for around $1 per pound, while polyhydroxyalkanoates (PHA), the larger category of biodegradable plastic which includes PHB, sells for about $3 per pound. Dr. Schauer-Gimenez laughed: “Even our Berkeley friends who are environmentally conscious won’t pay $3 a pound for plastic!”
By the time our meeting was over, I had realized that investment in scale-up was not trivial. Without going through this process ourselves, it would be difficult to realistically project price, yield, and environmental impact of our latex manufacturing method. This meeting also reinforced the message to our team that we will not be able to influence manufacturing practices unless we can sustainably sell latex at or below prevailing market prices.
We next met with Murthy Konda and Binod Neupane of the Joint Bioenergy Institute (JBEI) Techno-economic Analysis Team to get advice about how to predict and assess the feasibility and sustainability of our latex production. Dr. Konda and Dr. Neupane reaffirmed the difficulty of projecting yields, price points and environmental impact when beginning an unpredictable scale-up process. They explained their strategy: the techno-economic analysis team sets a price point (or carbon emission) goal for an overall process, and then they develop a computational model to establish the thresholds that individual project teams must meet to achieve that goal. They encouraged us to set goals based on maximum lab yields and standard industrial operations costs and adjust from there.
Taking Dr. Konda and Dr. Neupane’s advice, we decided to develop a vision of our end goal: if we were going to compete with natural latex, priced at less than $1 per gallon, then we would surely need to operate on a massive industrial scale. We set up a meeting with Jeff Davis, Head of Operations and Engineering for US Biologics Process Development at Genentech. I (Amy) asked him if he could help me predict, based on gross assumptions about the scale-up process, what we would need to run an industrial-scale latex bio-manufacturing facility and what price we might expect to set for our latex. He told me that a facility supporting 2,000L fermenters would likely cost around $200 million, while a facility supporting 25,000L fermenters would cost around $1 billion. He helped me develop a back-of-the-envelope estimate: a 25,000L bioreactor facility operating at full capacity could probably produce our polymer at close to $2-5 per gram. This would be far outside our goal price of $1 per gallon. (This estimate was, of course, based on experience with pharmaceutical production, which involves a more complicated series of testing and purification steps. Even so, we took this into account to produce a more generous estimate.)
Even at this massive scale, it is unclear that our latex production would be environmentally friendly as compared to traditional farming. Genentech uses a huge amount of water: judging by their 2015 corporate sustainability letter, their water usage is equivalent to that for roughly 10% of households in San Francisco County.23 Of course, Genentech has a massive facility that produces large amounts of pharmaceuticals, and based on my conversation with Mr. Davis, the same processes that ensure the purity (and safety) of pharmaceuticals seem to be some of the most water-intensive. (One can tell, too, from the corporate sustainability letter, that Genentech takes water usage goals seriously.) However, in the case of materials manufacturing, for which environmental sustainability would be an intended selling point, this level of water consumption might not be justifiable.
Finally, we met with Michael Lepech, Assistant Professor of Civil and Environmental Engineering at Stanford University, who has expertise in life cycle analysis (LCA) and has conducted research with NASA on the use of biomaterials for construction. Professor Lepech left us with two key takeaways. First, he emphasized that the environmental impact of a process is inextricably linked its energy source. Any bio-manufacturing facility in the US is mostly running on fossil fuels. Only about 13% of US electricity comes from renewable energy sources.4 Second, the production and distribution channels for traditional manufacturing materials have become so efficient that it is nearly impossible for biomaterials to compete on price alone. (I pointed out that localized manufacturing of latex might cut down on environmental and monetary transportation costs. In response, Professor Lepech pointed at my shirt: “Only about a dime was probably spent on transport for that.”) Because bio-manufacturing is so expensive and yields are so low, the market currently incentivizes bio-manufacturing of small, expensive products. Pharmaceuticals are the perfect fit, as are expensive, complicated materials (like Bolt Threads’ spider silk5).
What does the future look like for other biomaterials? Professor Lepech gestured to his work with NASA as a way forward. On a place like Mars, there is no market competition. Astronauts have only limited resources, and bio-manufacturing methods might make most efficient use of limited resources. It could be, then, that space exploration will provide the necessary incentives to develop biomaterials, incentives that our Earth market economy lacks. Once developed for space, Professor Lepech suggested, these materials might make their way back to Earth. Professor Lepech, whom we met through Stanford connections, had surprisingly led us back to NASA.
Our team ultimately integrated our research into the design of our project by reinvesting in the idea of developing space materials that might be repurposed in years to come. We came to appreciate the greater role that NASA plays in propelling research that might not otherwise happen. And in our meetings with the Stanford Space Initiative and with Dr. Alan Stern of World View, we attempted to better understand existing needs in space exploration that might be met by biomaterials.
(A side note: We also met with Dr. Stephen Comello, Associate Director of the Sustainable Energy Initiative at Stanford Graduate School of Business, who encouraged us to reach out to major rubber manufacturing companies and ask them how our technology might impact their operations and marketing strategies. We contacted Michelin Tires to ask them about their new sustainable natural rubber policy.6 We saw this policy as indication that tire companies might be looking for more sustainable sources of rubber, since natural rubber plantations currently contribute to deforestation and are susceptible to blight.7 However, we have yet to hear back from Michelin.)
References:
- NASA Office of Planetary Protection. (2016). Planetaryprotection.nasa.gov. Retrieved 10 May 2016, from https://planetaryprotection.nasa.gov/about
- 2015-06 Drought mailer BAY-South San Francisco. (2016) (1st ed.).
- Genentech Sustainability Data and Notes. (2016) (1st ed.).
- Electricity in the United States - Energy Explained, Your Guide To Understanding Energy - Energy Information Administration. (2016). Eia.gov. Retrieved 30 August 2016, from
http://www.eia.gov/energyexplained/index.cfm?page=electricity_in_the_united_states - Bolt Threads. (2016). Boltthreads.com. Retrieved 4 October 2016, from https://boltthreads.com/
- Responsible and Sustainable Managment of Natural Rubber. (2016). En.purchasing.michelin.com. Retrieved 20 October 2016, from
http://en.purchasing.michelin.com/Sustainable-Purchasing2/Responsible-and-Sustainable-Management-of-Natural-Rubber - WWF Statement on New Zero Deforestation Policy from Michelin | Press Releases | WWF. (2016). World Wildlife Fund. Retrieved 2 October 2016, from
http://www.worldwildlife.org/press-releases/wwf-statement-on-new-zero-deforestation-policy-from-michelin
