Did these scientists just create the first lab-grown human breastmilk?

Their press release was understated. “Two women may have made breastmilk — outside the body,” food scientist Michelle Egger and cell biologist Leila Strickland announced in a Medium post this past Thursday. The two founders of BIOMILQ presented the first evidence that they can grow breastmilk directly from isolated human mammary cells, housed in a sophisticated bioreactor. This may spell the beginning of the end for infant formula, and a new beginning for much other lactation research.

The understatement—the may—was a sign of cautiousness. Strickland and Egger don’t want to make false promises. They haven’t created a full replacement for breastmilk yet, after all, just a cultured version that contains two of the major components of the original: lactose and casein. They take the presence of these two major components to mean that they are on the way to creating milk nutritionally equivalent to breastmilk.

This is no small matter. Breastmilk is still widely considered the best way to feed babies, especially for the first six months of their lives, but many parents don’t have that option for a variety of personal and practical reasons. The popular alternative is infant formula, which has many benefits but can be a challenging adjustment for infants’ digestive systems because it relies on non-human proteins, often from cows’ milk but sometimes from hydrolyzed soy. BIOMILQ wants to become the next best thing when a newborn can’t be fed natural breastmilk—as digestible as human milk but as practical as infant formula.

Further tests are forthcoming, which could take the may out of the next announcement. However, BIOMILQ isn’t the only company working towards culture-based breastmilk. A day after their announcement, Singapore-based biotech start-up TurtleTree Labs announced that it would be presenting its own lab-grown mother’s milk to the public this spring. Other companies have announced similar ambitions. All the more reason for us to talk to these two vanguards of the cultured breastmilk revolution.

Since this is their first extensive interview, we wanted to know: how did they get involved with the mad plan to create breastmilk in a lab? How did they do it scientifically? Why do it anyway? And what hurdles do they perceive in the future, translating their findings out of a lab context into a generally available product?

Combining Forces

Egger and Strickland have been working together for just about half a year—they founded their company in September 2019—and, judging by the results, their collaboration has taken off like wildfire. They arrived at the same interest from different disciplines, but with similar convictions. Above all, they shared a desire to use their scientific knowledge to tangibly benefit people, and both of them had settled independently on helping them from the earliest possible age.

Egger is a food scientist by training and worked for a number of years at General Mills, where she invented new processing techniques and did consumer insight work, working on organic foods like the famous LÄRABARs. In this context, she developed an interest in the daily decisions mothers make about their child’s nutrition. This led to her starting an MBA at Duke University with an emphasis on social impact entrepreneurship, specifically food insecurity, malnutrition, and global food systems. Last summer, she worked for the Bill and Melinda Gates Foundation, researching “affordable plant-based protein sources for low-and-middle-income countries,” which deepened her interest in early childhood nutrition.

“During that summer at the Gates Foundation, I realized that the age at which I really appreciate kids—at three years old, when they have more of a personality—it was too late to help them. If we want to help the world, if we want to see babies grow up to be healthy, strong, capable adults, we have to be there from the moment they’re born. Breastmilk is a huge part of that.” That summer also exposed her to breastmilk substitutes, and the politics of formula suppliers, which she says, “value sales over the benefits of children.”

Egger knew breastmilk was the answer to setting every person on the right nutritional path, but it was also the problem.

By the end of that summer, Egger felt deflated. “I realized that even the Gates Foundation, working with the largest multinationals in the world, couldn’t move fast enough. The first 1000 days in a baby’s life are so vitally important to set the nutrition fundamentals that they will carry on throughout the rest of their life, affecting all their cognitive and physical abilities. For every year or two that it took us longer to try to get a project moving, millions of children around the globe were falling behind.” Egger knew breastmilk was the answer to setting every person on the right nutritional path, but it was also the problem. A new alternative to breastmilk was needed.

Serendipitously, this is precisely when she met her BIOMILQ co-founder Leila Strickland. The cellular biologist had been interested in growing breastmilk in a lab for some time and had also arrived at this interest from a combination of professional and personal investments. After getting her postdoc at Stanford in cellular biology, Strickland had two children; both were born prematurely and she had trouble breastfeeding them. This kicked off a search for alternatives. She knew there had to be a better option.

She found inspiration in cellular agriculture. Seeing Mark Post serve the first lab-grown burger at a press conference in 2013 was one such milestone. “It was pretty groundbreaking just in terms of my own thinking about what we could use the stuff of cell culture to accomplish.” Strickland started working on technology to produce milk from cultured cells, with the help of her husband. She pursued this ambition “at times as a garage hobby, in the grand tradition of tinkering, and at times as a full-throttle, furious pursuit of nothing less than the betterment of our health and our planet.”

Cellular agriculture non-profit New Harvest provided invaluable intellectual support. “They were really the first people who looked at us like we weren’t crazy,” Strickland recalls a meeting in 2015. “They were excited about our work. We had a super-invigorating call with Isha [Datar] and then attended the first New Harvest conference. They’ve been such an important influence on the field, and we made good connections there. We’ve continued the conversation with them ever since.”

Back then, Strickland says, “everyone looked at me strangely when I told them what I was trying to do.” But that has turned in her favor. “Even out here in North Carolina today, people know about cellular agriculture and cultivated meats, and are starting to get really excited about the possibilities.” Sensing this new widespread interest, Strickland started looking for a business partner to help her bring this technology into the world. “I met Michelle last summer, connected by a mutual friend in the area and in the field, and it’s been a really just incredibly natural partnership ever since. Our two backgrounds were a bit like puzzle pieces coming together. She’s been able to help accelerate this incredibly over the last few months and now we just feel like we’re on a rocket.”

The Way Forward

The speed of their success is less surprising if one considers the amount of expertise each of them brought to the table. “We’ve known for decades that mammary cells can be grown easily outside the body,” Strickland says. “It’s a common model system for breast cancer research. We also know a lot about those cells. We know that they’ll produce the components of milk when grown in culture on a benchtop scale.”

Aside from these basics, BIOMILQ is dedicated to solving an obvious but daunting problem: the cells are kept alive by a nutrient-dense liquid and, unless designed otherwise, would secrete the milk directly into it. “We needed a compartmentalizing process because we couldn’t serve people a mixture of milk and media. That’s been a guiding principle for our engineering.” That innovation, which separates them from other contenders in the field, is now patent-pending. “That was really the core insight from my background: understanding the process of secretion and how cells orchestrated spatially.”

The special thing about milk is its molecular complexity. It’s got a constellation of components that all need to be there at optimal levels in order to support the growth of the human infant, as designed by 200 million years of evolutionary pressure.

For these initial results, they started working with commercially available cell lines, specialized human mammary cells that can grow indefinitely under the right conditions, and expanded it in culture, before inoculating it in a bioreactor. “That’s a process that takes a couple of weeks,” Strickland explains. “The cells continue to grow and divide as in any standard validation culture system. One of the things that’s really beautiful about our product and our process is that we’re really focused on nurturing the cells and growing the cells to perform their optimal function. We don’t ever have to harvest our cells outside of this system. Our job is just to provide them the nutrients they need to do their jobs as well as they can. We’re in the business of taking good care of cells.”

Proof of Concept

Their attempt to recreate breastmilk is based on an admiration of its natural biology. “The special thing about milk is its molecular complexity,” says Strickland. “It’s got a constellation of components that all need to be there at optimal levels in order to support the growth of the human infant, as designed by 200 million years of evolutionary pressure. In order for something to be nutritionally equivalent, the complexity needs to resemble what we see in actual breastmilk.”

While their first proof-of-concepts highlight only two molecules in the myriad of nutrients, they see it as a sign that many more are there. “The reason that we think that our current findings represent an important milestone is because we’ve demonstrated the production of a predominant sugar and a predominant protein at the same time in the same system,” Strickland details. “I don’t think it would be as exciting if we had only produced lactose or if we had only produced casein, but the fact that we produced them both is indicative that we’ve turned on multiple pathways required for milk biosynthesis.”

Moving forward, they plan to use more sophisticated methods to analyze their sample, like mass spectrometry, which will vaporize their milk and detect the masses and charges of all the individual components within the cellular product. “We expect to be starting to run some of those samples in the next couple of weeks,” Strickland explains. The two scientists will consider their proof of concept experiments complete when they can identify all the different sugars, proteins, and fats present in their milk.

If the nutritional profile is as expected–equivalent or near-equivalent to natural breastmilk—scaling up will be the next step. Cell culture isn’t cheap, but BIOMILQ is confident about their economies of scale, especially since they’ve been using off-the-shelf components and cells so far. “We’re using systems that are made to be used with all types of cells that are not specifically purpose-built for this use,” Strickland says. “And so we have a number of sorts of customizations to explore in terms of their effects on optimizing this process. We have a lot of exciting ideas about how to upregulate the process of milk production.”

While their main goal is to recreate breastmilk in all its components, they will not be deterred if these initial samples have their own particular character. “One of our academic advisors who we spoke with about this was really optimistic about that exact possibility. He said that every failed experiment is a new product because there might be babies out there who are allergic to that one component that you’re missing. One thing that is worth noting is that milk itself is a really dynamic substance that just differs a lot from woman to woman, and from day to day, based on factors of her own biology. We expect that the nutrient content of our milk will fall within the range of what is observed in a normal population of breastmilk.”

The Next Steps

Egger and Strickland are excited about the potential research avenues opened up by their innovation. “We’re talking about a new way to grow mammary cells,” Strickland says. “It offers the possibility of studying lactation and human milk in a way that hasn’t been available to the research community in the past.” With their system, they hope to both produce breastmilk alternatives and further our understanding of natural breastmilk production. “I think that mammary cell differentiation, milk production, milk composition changes over time are all really interesting research questions that can be addressed at a system level using our process.”

People with compromised digestive functions could benefit from drinking human milk as a source of nutrition with more bioavailable nutrients.

The next step for the product is animal trials, and then, eventually, human trials. As one may expect, trials with newborns present unique challenges. Luckily, the two scientists intend to start by doing safety work with adult populations. “We’ve been advised that folks who have compromised digestive functions or are immunocompromised could really benefit from drinking human milk as a source of nutrition with more bioavailable nutrients,” Strickland says. Other adult beneficiaries could be people who have trouble with their intestinal lining.

These proposed adult uses of breastmilk are one of the reasons there’s such a large black market for it. “Currently, the only source of human milk is a lactating woman,” Strickland explains. “For the most part, babies need all of the human milk that lactating women produce. And so there’s not really ever been an opportunity to evaluate the possibility of human milk as a nutrition source for people who are perhaps geriatric or immunocompromised or have to compromise digestive function.” While these studies will focus on safety for newborns, it may also have the bonus of expanding the populations they can help.

Aside from regulatory challenges, the decisive question is how to grow this breastmilk cost-effectively at a marketable scale. “We want to optimize the process and proceed to a place where we had a line of sight to scalability,” Egger says. “An exciting part of our technology is that our unit economics basis is not that far off from where we need to be in order for it to be affordable for a lot of moms.” BIOMILQ is currently looking to raise a seed round of funding to support these efforts.

Their current bioreactor contains approximately as many mammary cells as a human mammary gland, except these cells have a major key difference. “A lot of our ability to scale is going to revolve around the fact that there is a lot of negative regulation of lactation within the body because the body has to balance the compromise between the mother’s needs and the baby’s needs,” Egger says. “Milk production is actually shut down in the body most of the time so that the mother is not spending all of her energy to produce enough milk that will never be consumed. Since we only care about the needs of the cells, we can produce milk all the time. Cells don’t sleep.”

Egger and Strickland do not see their product as a complete replacement of breastmilk. “We’re trying to be nutritionally on par with it,” Strickland says. “We don’t intend to replicate the sort of immunological properties of breastmilk or at least immunoglobulin. Some of the microbiomes that come from maternal inference transfer during breastfeeding itself are not something that we or that our products would replicate. Some advantages of actually feeding the baby on the breast are likely to remain. However, our product will be vastly nutritionally superior to infant formula and will offer women a way of feeding that’s nutritionally much better for their babies and, and quite a bit more realistic for them.”

With all this excitement, it’s easy to get carried away, but Egger and Strickland are resisting that urge. “We want to be sure before we tell moms out there that we’ve made milk,” Egger explains, “We want to be sure the science is right.” As BIOMILQ accelerates towards their cell-based breast milk, it’s clear that these two scientists will make sure that mothers and newborns are in good hands with the best nutrition mother nature has to offer. Their outlook remains cautiously optimistic. “We hope,” Strickland says, “to make a bigger announcement soon.

This article was originally published on Massive Science by Joshua Peters. Read the original article here.