What should we target when biomanufacturing food at scale?

Drafted in response to a prompt by Amir Barin on this LinkedIn post:

What's your take on the infrastructure bottleneck versus the technical optimization challenge?

I know it is easier to spot and state a problem than to figure out winning solutions. In my defense, such solutions usually follow a clear problem statement. So please bear with me :-) 

 A few years ago, I landed on "solve the demand problem and supply will follow." Absent waiting for an intrinsically fragile/unsustainable system to threaten supply of its incumbent products, the next most urgent need is to demonstrate compelling product(s).  Silicon Valley backed the idea that technology can deliver product breakthroughs in food that match expectations calibrated on iphone-level market disruption. If so, then robust - and really large! - demand would resolve investment and supply concerns. Capital would flow to meet demand and grow the investments. (This sets aside the very real concerns about lead time of course).  However, at 15+ years since founding Impossible, Beyond, JUST and others, that demand level doesn't exist.  If it did, money to enable “steel in the ground” would already flow and be gaining momentum to claim a proven market of this size. 

Therefore, consider the possibility that it is not possible to create products that are more compelling than those currently produced from animal tissues or secretions. In contrast to the framing of audacious Valley investors and innovators, what if there is no such thing as "better than beef?" As a hopeful technologist trained to think critically, I am sad to ask whether my long-sought goal of creating "the Doritos of beef" will always end up as some version of Hamburger Helper.  Despite what they’ll enter into a survey - and given expert blends of salt/fat/sweet/savory - maybe the number of consumers we require to adopt new alternatives most often just shrug and ... go with what they know instead.

If we assume that current products are about as good as they are going to be, or can be, then innovations in product and positioning will only get us so far. What we need isn’t “better” if that perception and preference can’t exist for consumers already imprinted on traditional animal product offerings. What we need is “cheaper and just as good” or at least a new and acceptable standard for newer generations. In other words, to be blunt, set the stage for a to sustainable futures: 1) herds and flocks their producers succumb to environmental consequences; 2) unreachable consumers are replaced by those raised on newer food products. 

This reasoning now leads back to the original question. In both cases, what we need is cheap and comparable. Here I am just guessing, but to me this means that we address the following technical problems, which are in some instances interconnected: gas and nutrient transfer, ideally without introducing additional shear; inexpensive and effective control of contaminating bioburden*; complete flavor neutrality of producer organism(s); relatedly, products that abrogate off-flavor classes in existing feeds (“maskers”); process robustness to off-flavor evolution; intrinsic limits on growth rates and, relatedly, cheaper feeds**. 

 

* This, in combination with improvements in gas/nutrient transfer, may enable access to far cheaper commercial fermentation systems. I get that this is a big lift. 

 

** Especially true for “cultivated” or cell culture approaches to creating food at realistic costs and scales.

Stories for Odin: what the NASA analyst saw in storms at Jupiter's north pole

These are stories I make up for Odin as he falls asleep. Usually he asks for specific features. Tonight I was given free reign.

Tonight's story is about the planet Jupiter. First the real part, then the made-up part.

Do you remember which planet is Jupiter? It is the fifth one out from the sun. Sometimes Jupiter is called a "failed star" because it's like our sun but much smaller. This means it can't light up. However, it is much, much larger than our planet, and we think made up mostly of gases. As it rotates, the atmosphere forms bands that move in opposite directions. This creates swirls at the boundaries.

Our government agency NASA, the National Aeronautics and Space Administration, sent a satellite to look closely at Jupiter. It is called Juno. The probe orbits Jupiter in an unusual way, axially - north to south. This means we get our first good looks at Jupiter's poles, and they are very weird - swirls piled on top of each other. It's like all the mixing was shoved together.

Do you know what "dissipate" means? Remember when you wake up and have breakfast, then all you want to do is run around and jump and play? This is energy inside you that wants to "dissipate" -- to go from where it is to where it wants to be. Sometimes when this happens in gases or liquids, structures form. These structure make it easier to dissipate energy, and are called "dissipative structures." 

Odin here is the made-up part. 

During an axial orbit, mission control takes many pictures in sequence. One of the analysts saw something odd in them, but she couldn't identify what. She looked many times, but the part of her brain sensing a pattern wasn't talking clearly to the rest of itself. She used a tool; she overlaid the images to make an animation. The result puzzled her so she took it to a colleague who studies Jovian weather. Her colleague spotted the funny thing immediately: the directions of wind around the pole were obvious but the polar swirls weren't moving with them. That is, the storms seemed to be moving on their own, or more likely in response to unseen forces. They took the result to the broader team.

That team argued about the meaning, with arguments falling into three camps. First, that the storms showed signs of self-determination in movement. Second, that this was seeing what we wanted to see, and that simpler explanations were available. Third, that we didn't understand this observation, but that self-determination wasn't extraordinary.

There was no answer to be had. They decided to have some fun. Juno carried a backup set of communication devices. On the next orbit, they transmitted into the polar storms everything they imagined could interest sentience (Odin, this means a creature that can think): music, words, math. Then they waited for the next flyby.

They found Jupiter's polar storms arranged differently. A trident and a tuning fork. Another trident, rotated 90 degrees. Then a crescent. Even weirder, the analyst's overlays suggested that the storms were completely still.

Images coming from the next flyby stunned our NASA team: nothing had changed except the arrival of another storm, which had apparently disintegrated into the others. It formed what everyone took to be the shape of our number "2."

(Odin has been bored into sleep at this point, but the analysts work out the Jovian response to be "E = mc^2")

Odin Quotes

Things our son Odin said that amused or surprised me.

2017.04.15
Tonight Odin and I built a guitar out of tinkertoys because he asked me to air-play "Dueling Banjos."  Also at his request, he was dressed like a chicken. After adding a tinkertoy piece he said, "chicken helped."

2017.04.15
Odin: It's Saturday. We should make saturs.
Haley: What's a satur?
Odin: it's a pancake with red things in it. The red things are raspberries. Not the "PPFFFTH!" kind. The put on your finger kind.

2017.09
On their way to preschool, Haley drives over San Bruno mountain in order to take in the spectacular views and greenery. The mountain is mostly covered with scrub brush, interrupted with the occasional tree stand.  In her rear view mirror, Haley sees Odin looking thoughtfully out the window for a long time.

Odin: Mama, does grass grow into trees?

2017.10
(In another car trip over the mountain)

Odin: Mama, do rocks grow?

2018.01.17
(Our dear friend "Uncle Martin" left after his semi-regular Friday dinner visits)

Odin: I want Uncle Martin to live with us. This is the last time he will leave. The next time he comes to dinner, he lives here.

2018.02.20
(Odin's closest friend is a girl his age named Leila. Their bond is strong and consistent to a unusual degree for their age. This dates to his first few months in preschool 2.5 years ago; he recently turned 4)


Odin (unprompted): Mama, Leila and I have known each other for a long time. We were holding hands before I was in your belly.

2018.02.22
Odin: What does "outstanding" mean?
Haley: It means unusual, in a positive way. There's good, then great and then outstanding!
Odin: Oh. I thought it meant "not having feet."

2018.03.10
(walking upstairs from rotating the laundry)
Odin: Dada, do stairs always go up?

(earlier, with Haley)
Odin: Mama, is the past always behind your back?

2019.03.30
(looking at a picture of Spongebob Squarepants fiercely riding a bike)
"That piece of cheese is struggling with his motorcycle."

2019.04.30
"Do black holes ever get full?"

2019.05.02
"Do anteaters also drink ants, or do they just drink water?"
"Is infinity more than a trillion, or less?"
"If I wanted to lift a church, I'd need a trillion people. Maybe the whole world."

 

2020.08.28

Me: "What is Mama doing?!" 

Odin: "She's pouring water on that plant." 

Me: "What?! Why would she do that?" 

Odin: (clearly doubting my sanity) "...so the plant's roots can take it up." 

Me: "Why does the plant need water?" 

Odin: "It mixes it with sunlight and air to make food." 

Me: "Oh. Well, I'm hungry. I'll slam some water, step outside and breathe. Sound good?" 

Odin: "...no. You're not a plant." 

Me: "But I eat plants." 

Odin: ... 

Odin: "You are confusing and full of nonsense." 

In support of removing the stigma around anger and replacing it with a toolkit

Haley and I often discuss how to interact with emotions as parents (ours and the boys'). At least in my world there have been strong proscriptions against the legitimacy of expressing anger. It's taken sustained effort for me to support rather than stigmatize - often with zero conscious thought - "negative" emotions in our family.

Obviously, as an adult, we can't throw tantrums or scream at others and expect to thrive. I'm not saying that we do or should cultivate this in our boys. On the other hand, anger and sadness happen regularly. That doesn't stop with age. So I try to do better than shaming emotions as disallowed, or telling them, effectively, to shut up and get over it. This category of response isn't strategy; it is a demand for an outcome without guidance for how to achieve it. When I realized that, it became obvious that silencing and shaming were failures of parent-as-teacher and therefore of my own understanding of how to deal with anger. The impulse to silence Odin's anger arose from not knowing how to interact productively with this emotion.

So, this passage in a 2014 Slate article stood out to me:

The violence that is a part of anger disorders is fueled by chronic repressed rage that has found no socially acceptable outlet. It is fostered by families in which adults behave in violent, intimidating ways or in which anger is tightly repressed. In either situation there is no appropriate model for the safe or constructive expression of anger.

Adding that, in the absence of productive strategies or support around emotional education, you obviously do better releasing your children into the wild with some ability to modulate the expression of rage. I assume that repression is more functional than for example throwing punches and screaming in the workplace.  Here I just wanted to highlight that better tools than repression exist.

Stories for Odin: where the dragons of Brisbane came from

These are stories I make up for Odin as he falls asleep. Usually he asks for specific features (eg "something I've never, ever, ever, ever heard before" or "the one where butterflies turn into dragons, but only with me and Dada"). I take it from there.

 

Kid version

One day a butterfly flew down from the mountain. We had spilled some peanut butter and honey on our picnic table. The butterfly ate some. Then something started to happen! The butterfly got bigger - like a lot bigger! Its wings grew and spread out and its body did too. Soon there was no butterfly anymore but a huge dragon. Its wings beat down and it went WHOOSH WHOOSH WHOOSH when it started to fly up. 

The dragon looked down at you Odin with eyes that look like outer space. It said "Hello Odin. My name is Pomba." You two became good friends.

Non-kid version

The Mission Blue butterfly is native to San Bruno mountain. Near the peak of the mountain lives a very large family of these butterflies, feeding on lupins and sunflowers.  Sometimes, when the east bay is hot enough, huge bodies of air are drawn over the mountain. These bring with them the marine layer we see brushed over the top of the mountain from Brisbane. When enough air gets pushed over the mountain, we feel it as strong winds.

One day, winds brought a butterfly down to our back yard. It was confused and hungry. We had left some peanut butter and honey in our back patio. He licked both, as much as he could.

It turns out that peanut butter and honey cause butterflies to change. The butterfly's wings grew larger. His blue color faded to green and grey and brown, and his wings thickened. Bones like fingers grew through the new membranes .

We were sitting on the steps while this happened, amazed and alarmed. This butterfly grew huge! Its mass began to crack the picnic table, so it began to move its new wings (carefully at first). WHOOSH. WHOOSH. WHOOSH. Air flew past us while the massive body lifted slowly up to land on the roof.

Now with a long neck, a small dinosaur head and thick leathered wings, we realized that our butterfly had become a dragon.  His head craned down to look at us. You taught him to say "hello." He liked it when you pet him and purred like a very loud kitten.

You named him Pom Pom, but his nickname became Pomba. You became very good friends, bonding especially over piles of noodles left steaming on a Clement Street rooftop for area dragons. 

Only much later did we realize that Pomba's eyes were full of stars.

A comment in support of #metoo, and good parenting

I watch the #metoo posts accumulate in my feed with sadness, because each instance represents trauma and unfairness, but also optimism, because each represents an individual decision to speak up. Speaking up can introduce badly needed personal reality into an often fictional social reality. 

I've deliberated about whether to say anything in support or response. On the one hand, these are statements of an experience from which I'm largely exempt due to gender privilege. Who am I to jump in and say anything? For instance, what if statements by males appear to confer legitimacy instead of the intended support? Women are speaking up about their life - let's listen. On the other hand, as other women in my feed suggest, silence can appear unsupportive. So, fuck it. We can all do nuance, or learn to.

In line with another friend's response, it's extremely important to recognize, highlight and change the reality of harassment and discrimination that my friends are communicating. Hopefully, social media campaigns will help to do this. 

I say this knowing that I've been a part of the problem, both actively and passively. I'd like to think that I've been able to recognize and improve on my own bias, and to openly discuss discrimination against women as a route to change. But maybe not. And if not, I am happy to witness, listen and/or discuss from a posture of respect. I encourage all my male friends to do the same.

One of the most powerful forms of civil disobedience is raising children well. There's a lot to unpack in that statement, with important caveats. Still, for those of you broadcasting your experience as women, and if it matters to you, raising our boys to respect everyone - and particularly women - is front and center for me.

How to talk to "opponents" about politics, and why I think you should try

This talk lines up with a broader conversation I want to promote. Engagement - specifically about politics - is the primary means we have to create systematic change. The oft-bemoaned "polarization" is in my opinion a pain point on the way to a more functional citizenry. Polarization reflects a lack of skills required to best use a very powerful technology platform. Because skills can be learned, I'd rather be here than to not have the platform.

Want to make the country better? Engage those you expect to disagree with you. Bring a hot beverage and be prepared for some discomfort on your way to building a better world .


Here's a related set of ideas, with minor issues.* 

A common complaint I see regarding political discourse via internet is that we either self-select for those who agree with us or fall into offense/defense mode. However, it may be that in grappling with this we effectively use technology platforms to disseminate more emotionally effective and mature means to interact with conflict. I'd like to think that we turn a current negative into a net positive, if you view, as a positive, the frank and calm evaluation of political positions on their factual merits.

* finding common ground for the purpose of winning someone over might work, but is a distant second to internalizing that we all actually *are* in the same boat and even suffer from the same kinds of biases and defenses. A strain of this (just one example) is the irrational use of "rationality" to assert rhetorical dominance. In my view, this is simple aggression (ie, irrational if the goal is to create change) and will thus spark a defensive posture in most recipients. Asserting rationality - here, dominance - isn't partnering with someone in order to dissolve a potential conflict. And it isn't recognizing them as human, with shared foibles (that the aggressor may not happen to suffer at the moment). It's trying to win, which aside from friendly verbal sparring, arises from viewing someone as "other." This is tribal.

Also not thrilled with communicating "tribal" using cartoonish Native Americans, but I get that it visually communicates the point.

Stories for Odin - 1

These are stories I make up for Odin as he falls asleep. Usually he asks for specific features (eg "something I've never, ever, ever, ever heard before" or "the one where butterflies turn into dragons, but only with me and Dada"). I take it from there.

The Spider of Saturn
January 2018

(Inspired by the recent ending of the Cassini mission)

Along the visible rings of Saturn there lives a creature made of energy and specific kinds of matter. This is Saturn's Spider.  It looks exactly like Saturn's rings, but hunts and harvests magnetic particles from the ring as it moves along them. In its path the Spider leaves fine particles entrained to the same energetic field; this is its web.  The Spider also stitches the particles into itself using energy from the solar wind.

We talk about how the Spider traverses its rings. It's not a movement you or I could see. It moves very slowly. Solar energy is dilute at Saturn's distance from the sun, and the Spider, feeding on it, hunts with corresponding slowness.  Any action, even a frenzy of rapid feeding, can take months.

Every 30 years Saturn completes an orbit around the sun. When this happens the Spider trains its attention in the direction of Earth, spreads itself out thin, and listens. Its web acts as a large antenna and its body encodes what it hears. The Spider has been doing this at the same orbital position for millions of years. As Saturn moves away from this position, the Spider taps its encoded message into its web. The web resonates across the entire ring system with the new encoding.  When the web is queried by pulses of radiation from outside the solar system, it transmits what the Spider has written into it. The web has a large surface area, making it easier to see from very far away.

The Spider sews its web and charges it with information from Earth because this is what it was placed into Saturn's ring system to do. Hundreds of millions of years ago, the Spider's creators recognized Earth's potential to create information processing capacity. The timing of that capacity is very difficult to predict, so the Spider was asked to watch our planet for its emergence.

Why Dragon Eyes Look Like Starfields
2/20/18

(Odin requested story with: dragon; Odin; friend Leila; Dada; not little brother Alder; our backyard play structure; and a slide. In my stories, he calls his dragon friend "Pom Pom" but says its nickname is "Pomba," so he stipulates that we call it by the latter name)

Odin and Leila are playing on the slide while Dada watches from the play structure. They roll different items down this slide, trying various balls we have on hand: volley ball, golf ball, baseball. Each works -- will they move at different speeds? We will test this later. They find that a football does not roll well. We think this is by design.

After watching a set of plastic trucks barrel down the slide, Odin tells Leila that he would like to fly with his friend, a dragon named Pomba. As it happens, Pomba lives in a ravine near the top of San Bruno mountain. Like all dragons, Pomba has excellent hearing. He heard Odin's request, and soon a familiar shadow passes over the house. The dragon spirals down, then beats his massive wings to slow his descent and land gently on the roof. Leila and Odin sit on the steps near the slide, looking up over the patio at the dragon. Pomba extends his long neck, bringing his head level with Odin and Leila's eyes. The rest of the dragon hasn't moved -- that's how long his neck is! He says "Hello, Odin. I am happy to see you again. Did you want to fly with me?"

Odin looks into the dragon's eyes and notices, for the first time, that his friend does not have eyes like his own. Instead of a pupil and iris, the dragon's eyes are a dense field of points of light on a black background. They remind Odin of starfields he's seen in Astronomy magazine sent by Grandpa Bob. Pomba's eyes are littered with points of light so dense, with so much to see, that even though nothing moves everything still seems to move. There is too much information to take in that area appears newly seen each time. Odin and Leila look into the dragon's eyes for a long time.

Odin asks the dragon why his eyes look like stars. 

The dragon says, "This is how dragons make fire. People say that we create it in our bellies, but really we ask for it from stars. Our eyes can connect us to any star we like. We open a window to its fire through our bodies."

Odin and Leila are excited, and ask to see dragonfire. Pomba replies that it is not safe even to look at unless it is from very far away. Dragonfire is actually a direct window into a sun. It is so bright that it will damage their eyes up close - even if they look at it quickly. Odin remembers how bright even the eclipsed sun was last summer, at Grandpa Bob's house. He asks how they can see dragonfire safely. Pomba asks them to wait.

The dragon beats his massive wings and lifts himself slowly from the roof. Odin and Leila smell his hide in the air as he rises. Soon, Pomba has flown very high. Odin thinks he looks like a piece of dust in the sunlight, or an slow-moving jet.

Suddenly there appears a flash so bright that Odin and Leila have to shield their eyes! A searing white line extends from the dot of a dragon, then streaks across the sky, into space. They see a solid beam on the inside, but it is decorated with flame along its length.

When Pomba returns, he looks very sad. Odin asks him why. The dragon says that when he creates starfire, the stars he touches are terribly eager to speak with him. They are separated from anything like themselves by great distances, many light years ("Odin, this this is the distance traveled by light in a year"). Their light messages can't travel the distances any faster. But when a dragon asks for starfire, they always give it happily in exchange for the company. He feels them ache for companionship. The loneliness of stars is why all dragons become very sad whenever they make dragonfire and why they do this so rarely.

Dragons can touch stars that cannot touch each other because dragons are born eyes that can develop into wormholes. These fold the distance to any star they conceive and decide to contact. (because, sure -- that's how wormholes can work)

Woman jailed for letting her kid play (unsupervised) in a public park

Here is the news story with commentary here. I followed the link to find that, as of 1999:

1) 70% of all US children were 11 years old or younger.

2) this group (<=11 yo) accounted for ~ 50 stereotypical kidnappings and ~ 10,000 "non-family abductions."

3) there were 2.5 times as many children older than 11 years old who were so abducted in 1999.

4) given the child population of ~70M in that year, and unrealistically assuming uniformly distributed risk (it's not), means that children under 11 would have a 1 in 10,000 chance of being abducted in the broadest sense of this study's definition and a 1 in 1 million chance in the stereotypical sense.

By comparison to the larger of these abduction numbers for <=11 year-olds, in 2010 roughly the same number of children died due to medical complications and about half this number died simply due to being in a car. These numbers include children up to 19 years old, so it's not a completely fair comparison. But I still think it makes the point: if you're against healthcare reform and are willing to put your child in a car, there's no rational basis for calling the cops on this woman. In various online conversations I continue to post these and related mortality data because discussions about children rouse people's emotions, including my own, and data is helpful to ground/anchor one's sense of real risks.

What favors the evolution of drug-like molecules?

Placeholder - I've suggested to ASM that one session next year cover whether and how multicellular organisms exert selective pressure that favors the evolution of drug-like natural products. I plan to write more about this more, here, but for now this is what I submitted to ASM: "Small molecules (natural products) transformed the practice of medicine, but we do not understand what evolutionary pressures yielded their important biological activities. In the case of commensals and primary pathogens, the host itself likely provides selection. How do natural products alter the host to favor colonizing microbes? Understanding this dynamic will crucially advance the prediction and measurement of novel activities." I recommended these speakers: Michael Fischbach Nancy Keller Gillian Turgeon Christian Hertweck Johnathan Walton Any others you recommend for the session?

High-throughput scoring of yeast growth. Well - using 96-well plates, anyway

This is fantastic. Can't wait to get into the lab and try it out! High-resolution Yeast Growth Curves in 96-well Plates Abstract: To compare effects of screen compounds on various yeast strains, YPD yeast cultures were seeded from single colonies and grown overnight to saturation. The resulting cultures were diluted to approximately 1000 cells/µL and grown until log-phase was reached (absorbance of 0.6–0.9 at 600 nm). The log-phase culture cells were collected by centrifugation and washed twice with sterile water to remove the YPD media. The resulting pellet of cells was resuspended in the appropriate liquid media for the experiment. Cultures of 150 µL (1000 cells/µL) were deposited into wells of a 96-well round-bottom polystyrene plate. The plate was lidded and incubated at room temperature with continuous shaking and automated recording of the absorbance (600 nm) every six min. We did a high-throughput screen last summer to evaluate activities of our pilot natural product library against millions of gene-gene interaction pairs in Saccharomyces. The idea was to map any activity of these compounds onto specific gene products (proteins). We have some intriguing leads that, if confirmed, could shed insight on the biology of the producer pathogen. The linked article article confirms my hopes that we can test whether hit activity reproduces in a high-resolution assay.