Human Milk

From the transfer of stem cells to insights into cancer research, the science (and sales) of human milk
29 March 2022
Presented by Julia Ravey, Chris Smith
Production by Julia Ravey, Anoushka Handa.

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Human milk is the special subject we’re looking into this week, including how the cells it contains can jump into a baby’s bloodstream - and literally make mum part of their offspring. We hear how biotechnology is aiming to produce human milk in the lab as an improved alternative to formula, and how donated human milk is helping sick babies, parents in need and cancer research. Plus, we dive into why online sales of human breast milk are on the rise due to a slightly surprising consumer group…

In this episode

A cartoon of the Earth as a coronavirus particle.

01:08 - "COV-erview" of the latest COVID-19 wave

An update on how ever lighter pandemic measures are coping with spread of the virus

"COV-erview" of the latest COVID-19 wave
Paul Hunter, University of East Anglia

Reporting has gone quiet on the “Covid front”, largely because of what’s been happening on the “Russian front” in Ukraine. But a quick glance at the “daily dashboard” or the Office for National Statistics breakdown reveals that cases are at an all time high: roughly one person in every 15 is infected. So, as further booster doses begin to roll for the over 75s, adults in care homes and anyone over 12 with an immune problem, we thought it was high time for a Covid update - a “cover-view” if you will - to explore what’s happening and why, whether the current - very much hands-off - approach to management of the pandemic is the right one, and what the future likely holds. Chris Smith spoke to Paul Hunter, who is an infectious diseases specialist at the University of East Anglia…

Paul - The problem at the moment is that a diminishing proportion of people who are infected are actually going for a test. For England, for most of the pandemic, we've been picking up about 40 to 45% and, in the most recent data from the ONS, that was down to about one in eight.

Chris - So, in other words, there are eight times more infections out there in the community than the tests currently being reported suggest.

Paul - Yes, and probably a bit more than that as well.

Chris - The numbers that are being suggested are already pretty high. I mean, if you look at the government's daily dashboard, and then you look at what the seven day average would suggest is the daily rate, and you times that by eight, that's a stupendously high number.

Paul - It is. And this week it is almost certain that the number of real infections that are going on in the community are as high, if not higher, than they have been at any time in the pandemic.

Chris - Now what's underpinning that. Is that, as Chris Whitty and Patrick Vallance said at the Downing Street briefing, when they unveiled the withdrawal of a lot of the measures, just because more people are going to meet more often? So we're expecting more cases or is there more to it?

Paul - I think there's more to it. There was a huge Omicron wave around the world, and there is now a subsequent second wave going on. That second wave is due to the sub lineage of Omicron, the BA.2. That's the thing that has been increasing in the UK since Christmas. But, on top of that, from about the 1st of March, we also saw that increasing and accelerating. That was almost certainly due to behavioural change, partly due to relaxation of the remaining rules and probably also as well because people are mixing more over the last few weeks.

Chris - Is it translating into more severe disease, though? Or are we seeing cases, but not seeing consequences?

Paul - We're seeing hospitalisations rise. The issue is, at the moment, a lot of that increase is in people who are in hospital with COVID rather than because of COVID. In over half of all infections in hospital, the infections are not the reason for the person being in hospital. It's an incidental finding.

Chris - In other words, you've got loads of disease in the community, people are going to continue to have heart attacks and strokes at the same rate they always have. So, inevitably, if you've got lots of COVID about, you're going to be admitting people who also have coronavirus.

Paul - Indeed.

Chris - If we look at perhaps the most sensitive measure of severity, which is how many people are on ventilators, that number appears to be lower than it was last July when we were busy opening up the country saying, right, freedom day is finally here, we've got far fewer people in intensive care beds. It's about 200 or so, we had double that number last year.

Paul - Absolutely. That's starting to drift up a little bit because of the number of infections. But you're quite right, the proportion of people in hospital who are actually in an intensive care unit bed is substantially lower than it has been throughout the entire. There are signs that the infection isn't being as severe as it has been in the past and you can see this in various other metrics, however you want to play it out, that the proportion of people who die is lower than it's been throughout the pandemic and it's probably lower now than you would expect to see from seasonal influenza.

Chris - So are we managing this the right way at the moment in your view?

Paul - There's a lot of issues going on here. The first is that we do know that immunity to infection wanes after vaccine, or even after an infection, you can get another infection, although generally those second infections are less severe. The concern that I have is that the longer you leave it between infections, the less protection you have against severe disease. We see this with influenza. If you live on a remote island and you experience flu once every 10 years, then you often have higher fatality rates than when you get it where flu circulates every year. So, there is an issue here about how long is the best amount of time to apply these sorts of measures. I was only today, actually, reading some reports going back to 2006 by a World Health Organization working party on influenza control measures and, basically, the point that they were making was that a lot of these measures never prevent spread ultimately, but they delay it. And early on in the pandemic, delaying the spread was really important, partly to protect the health service otherwise it would've been overwhelmed, but partly because if you were able to delay an infection until the autumn, we knew about dexamethasone, our intensive care specialists were much better at keeping people alive. Then, of course, if you were able to delay your first infection or first exposure until 2021, when we had vaccines, then you were much less likely to die. But, once you've got all those benefits and nothing else is coming along, then actually the value of continuing restrictions becomes a lot less. The balance between the harm that these sorts of restrictions can do to people's mental health, to the economy, and all these other things related to the benefits in terms of reducing spread of infection starts to shift.

Chris - Do you foresee that we will manage this in the future a bit like we do the flu where we've got this international surveillance system running, we watch what the flu does, we try to preempt its next move and we bottle that in a vaccine, we give that to vulnerable people in the autumn, and we hope we've protected them for long enough for the flu to come through a country and then exit the premises, leaving behind people who may have had a brush with it, but they've been okay? Is that probably what we're going to do for COVID?

Paul - To a large extent, yes. Over a year ago, Nature magazine did a survey of leading infectious disease researchers, and the vast majority of them accepted that this was going to be endemic, was going to cause infections repeatedly. But, over time, as people's immunity built up from both vaccination and natural infection, the disease itself would get less and less severe and become more mild. And, in fact, that's what we're seeing. Interestingly, we're in a situation now with Omicron, the value of vaccine is to actually help make sure you survive your first one or two infections, and after that, your immune system will make sure that although you will still get infections, they won't actually put you at risk.

Chris - Let's hope it stays that way. Paul Hunter, there.

lettuce crop in the soil

08:36 - Modified lettuce boosting astronaut bones

Space voyagers exploring new ways of getting their nutrients up

Modified lettuce boosting astronaut bones
Kevin Yates, Center for the Utilization of Biological Engineering in Space

Up into space now, and astronauts experiencing microgravity during prolonged stays in space can develop osteopenia, or weakening of their bones. This can be significant, with a loss of up to 1% of their bone mass per month. But Kevin Yates, part of NASA’s Center for the Utilization of Biological Engineering in Space (CUBES) programme, explains to Evelyna Wang, how he’s grown a genetically modified lettuce that could help prevent bone mineral density loss...

Kevin - We modified this lettuce to include a gene which instructs the plant to produce a fusion protein, which we call PTHFC.

Evelyna - This fusion protein is composed of two parts. The first is PTH.

Kevin - The PTH part regulates calcium in the blood and therefore regulates the amount of bone mineral density that you have.

Evelyna - The second part of the protein is called FC, a bulky component that they attach to the active PTH.

Kevin - And by adding that we increase the amount of time the fusion protein can stay in the blood, thereby increasing its expected efficiency.

Evelyna - So, your hope is to have this lettuce that produces and contains the protein that treats bone mineral density loss?

Kevin - That's right. So, either it may be possible that you can simply eat the lettuce, and get the dose that way, otherwise the protein can be extracted from the plant leaves.

Evelyna - Is this protein an existing medication? And how is it typically administered?

Kevin - As a drug, a portion of the naturally occurring human parathyroid hormone is an FDA approved drug called Teriparatide, and that is given in a daily injection.

Evelyna - So, why can't you just bring the medicine with you into space?

Kevin - So, for one thing, a primary concern is the amount of mass you'd have to carry to do that. As a rule of thumb, for every one kilogram of mass that you want to bring with you, you need 99 kilograms of support, power, heating and cooling, this sort of thing. The other issue is that cosmic and solar radiation can cause pharmaceuticals to degrade over time. But, if you just bring seeds to grow plants which will produce the medicine that you need, seeds are of course of a much smaller volume when you consider what you'll get out. And, of course, you can take these plants to the seeding stage and make more plants from the seeds that are produced.

Evelyna - Right. Why did you pick lettuce?

Kevin - We know that lettuce can be grown in microgravity. It's been done on the International Space Station. One interesting fact about lettuce is that it's seen as having benefits for psychological health, and that, for a long time spent in space, having a green leafy plant growing, and also as food, offers a lot of mental health benefits to astronauts.

Evelyna - Oh wow. So there are both psychological and medicinal benefits to this lettuce. Are there other applications you can use this lettuce for?

Kevin - Yes. I think that the fact that this works in the resource limited environment of a spacecraft, if it works there, it will work on earth. And there are a lot of places on earth where medicine of this type would be hard to produce because you need something like a bio reactor, which has to be temperature controlled, powered, etc., and sterile as well. But if you can simply plant a plant in the soil, or there's a greenhouse, or in a field, to get medicine, I think there are a lot of places that could benefit from that.

Julia - I am surprised he went for lettuce and not rocket, but there we are. Evelyna Wang speaking to Kevin Yates. He presented that work at the American Chemical Society spring meeting this week.

boa constrictor snake

13:45 - How boa constrictors avoid self-suffocation

Hungry boa constrictors need to ensure their unique hunting technique doesn't harm themselves in the process

How boa constrictors avoid self-suffocation
John Capano, Brown University

Now to another piece of animal news. When snakes like boa constrictors wind themselves around their potential lunch, their aim is to squeeze sufficiently hard that blood cannot get back to the prey animal’s heart, so it passes out, making it easier to swallow whole. But the snake’s got a problem: by squeezing that hard, it’s also potentially stopping its own lungs working, meaning it should be at risk of asphyxiation, shouldn’t it? From Brown University, John Capano explains to Chris Smith…

John - We were really interested in understanding whether or not snakes could actually breathe when they're constricting, because they're using their ribcage to kill another ribcage. Similarly, when they eat something, their ribcage expands. We've all seen snakes with really big food items in them and we were wondering, 'can they actually breathe when their body is swollen that wide?'

Chris - It sounds like a pretty obvious thing, but how do snakes breathe?

John - Snakes breathe with their ribcage. We as mammals are actually special in that we also use a diaphragm, but snakes and lizards only use their ribcages. They rotate the ribs, they make their chest bigger which then causes a pressure change, which then causes air to rush into their lungs.

Chris - And so how did you investigate what the snakes were doing then?

John - We originally were just doing some observational work. We were just watching snakes, constrict and feed, and we noticed that they were breathing with a different part of their body when they were constricting or feeding relative to when they were just hanging out in the cage at rest. It started with some electromyography called EMG. It's a technique that lets us measure the electrical pulses, running through a muscle. We found that the muscles that control breathing and pull the ribs, snakes can turn them on and off in different sections of their body with pretty good control. But that really didn't give us the resolution to answer the question we wanted. Then I actually applied to grad school and went to Brown in order to use this technique, X-ray reconstruction of moving morphology. It lets me look inside of an animal and see how the bones are moving inside a living animal. When I did that, I was able to use a kind of an experimental setup to prevent rib motions in one part of the body and then see if the snake would then shift it somewhere else. Analogous to what would happen during constriction or eating something really big. But we did a really controlled experiment where we could replicate it really easily too.

Chris - So what do they do then in order to avoid themselves asphyxiating when they're constricting things? How do they do it?

John - What we found is that snakes have pretty long lungs. In boa constrictors, their lungs are about 30% of their body length. In other snake species, they can go up to like 70 or 80% of their body length. But in these boas they have the front part of the lung where gas exchange happens, and then the back part, which is just kind of a bag. They normally will breathe in the front part. But then when we put the cuff on the front part and we compressed it down, they stopped using those ribs entirely. They just started breathing with the back part, which is really amazing because they're actually ventilating with the back region. They just switch and start breathing further back down the tube and drawing air through that part of the lung in the front, even if that part of the body is doing something else.

Chris - Is there not a sort of 'a chicken or egg' situation here then? Because in order to do this sort of behaviour that had to evolve for them to be able to do that in the first place, which then meant they could feed this way. How do you think this behaviour appeared in the first place?

John - That's the real difficult question of this study. It's really hard to tell which came first, the chicken or the egg in this scenario. Because you're right. Constriction and large spray ingestion require you to be able to breathe while you're doing them, so it would be really difficult for early snakes to exaggerate these behaviours to eat prey that's 100% their own body size. It's like me eating a cheeseburger that weighs 180 pounds in one bite. That would be really difficult if you couldn't already breathe while doing it. We think that this modular lung ventilation mechanism either preceded constriction in large prey ingestion or evolved in concert with it. Then the feedback of being able to breathe a little bit better, allows you to maybe constrict something a little bit bigger and then eat something a little bit bigger and then the feedback of having that ability would then allow you to exaggerate these traits even further. Considering that snakes are literally just a tube of ribs and that they really have this fine rib control, it may also be possible that this rib control may be one of the earlier traits of snakes. This ability to move ribs all along your body in order to push into the environment in different ways; That may have been turned into a ventilation mechanism, that may have come from a ventilation mechanism. But just because of the way snakes work, I think that this rib control thing was probably a really early trait within snake evolution. It's hard to tell which one came before the other ones, but maybe some future work will figure that out for us.
 

orangutan ape

18:31 - Orangutans make unique noises in big groups

Are these unique vocal calls an effort to stand out from the crowd?

Orangutans make unique noises in big groups
Adriano Lameira, Warwick University

How we speak is very much governed by the environment we grow up in. From accent, to slang, to language; our “group” shapes our communication style. And, after analysing years worth of audio recordings, it has now been found that social groups also influence the vocalisations of orangutans, with more original shouts happening in larger buffooneries. Julia Ravey spoke to lead author Adriano Lameira...

Adriano - As humans, we like to reserve our position in a special place among nature. Originally we were the 'tool user' or the 'tool maker' and now there are books with thousands of examples of tool use, like octopuses use tools and ants use tools. Then we moved on, 'okay, we're not the tool user, but we are the only cultural animal'. Turns out that that's also not the case. We're eating away how special we are and somehow language is our last reserved stronghold. The prevalent theory when we started was that unlike human verbal behaviour great ape vocal behaviour is innate, it's instinctive, it's automatic, it's reflexive, individuals have no control whatsoever, It just comes by instinct.

Julia - When did you actually notice orangutan noises were different across groups in the wild?

Adriano - That was right from the start. We started cataloguing the call repertoire of orangutans at one population and there were other populations relatively nearby. It was rather striking when, in one population, some orangutans would be doing certain types of noises when they are building nests. Then you go to a nearby population and they aren't doing those sounds, and then you visit another one and they do different sounds. We just had to start collecting the data and the evidence. That started almost 20 years ago.

Julia - What did you find when looking at orangutan vocal calls across these different groups?

Adriano - What we found was that there is a social influence. Each individual is being moulded by what he's hearing and who he's interacting with. We found that in high density populations, where there are many individuals living one with the other, that they really like to constantly produce novel calls. They'll do calls that were never heard before. But they'll do that once and then no one will adopt that new call because everyone is doing their style of things, so to speak. This turns out to be very distinct of what's happening in low density populations, where individuals encounter each other less often. What we see here is that when they communicate, they tend to go back to the same repertoire. In this sense, they can be thought of as more conventional, more conservative. What is interesting is that in the low density populations, although they are conservative and always go back to the same set of calls, where there is a novel signal, they do pick up that new signal and incorporate it into their repertoire, so their repertoires are more complex than the ones in high density populations.

Julia - Why do you think there is this disparity between the size of the populations and the number of original vocal calls? To me, it makes me think of a big city like London, where there's lots and lots of individuals, but they all live in their own little pockets. Is it like people are trying to stand out more?

Adriano - I think the parallel is a legitimate one. Once we start thinking that language is a continuous process and there are things that we share with great apes, when we start looking at the data, new parallels and similarities will show up. Maybe when we go to a big city or we live in a big city and when we dress in a quirky way, or we try to put our hair in a way that stands out, we may think that we are practicing our individuality and our free will and that those things are very human specific. Well now having similar data in evidence for our great apes, either that makes them more human or us more apes. In this way, I do hope that connecting us with our own larger setting will make us be more respectful and good stewards of the planet.

Julia - Yeah, I really love that. Seeing ourselves as an extension of other animals out there should hopefully enable us to be better at protecting the planet and these animals and their habitats.

Adriano - Yeah, exactly the same way as you respect a fellow human, you should adjust your respect to that animal.

Mammalian cells tagged with green and blue dyes

24:44 - Breastmilk stem cells pass into offspring

Stem cells from mice can pass into infant pups after feeding and integrate into many body tissues

Breastmilk stem cells pass into offspring
Gurkan Ozturk, Istanbul Medipol University

Breast milk is the special subject we are looking into this week, including how the cells it contains can jump into a baby's bloodstream and literally make mum part of her offspring. Chris Smith spoke to Gürkan Öztürk from Instabul Medipol University about this work. Before that, Julia Ravey explains the rise of online sales of breast milk, and a slightly surprising consumer group…

Julia - I am perusing the milk aisle in my local shop. Oh, there is actually spilt milk on the floor and no one's crying - good to see. For me, I'm not the biggest dairy drinker. I actually don't drink dairy at all. So for me, I like to go for an oat milk or a soy milk, but you know, I know people do like cows milk as well. But how do you feel about human milk?For some people it's right up their street...

JJ - I guess people know me as the breast milk bodybuilder.

Julia - Recently, a somewhat novel market has gained traction -  individuals selling human milk online. People's motivation for buying this body fluid vary, and we'll hear more from the breast milk bodybuilder later on in the show. But at the Naked Scientists, we thought -  how easy is it to get human milk delivered to your door? I took to the internet to find out... Let's see what this brings up. Human milk for sale. I can see some container bags with what looks like milk in them -  Breast milk, healthy. Let's have a look and see if I can actually get some of this. Buy it now. And this is with second class delivery, so it will arrive in approximately two to five days time. I'm going to contact the buyer to see if I can get it a little bit quicker. Oh, okay, that's sorted then. Paid for, and it should be arriving tomorrow. And once this arrives, I'm going to take it round to the lab to analyse it to see what is actually in this milk and is this method of transport safe? I honestly didn't think it would be that easy to get. Let's see what happens tomorrow.

Chris - Pretty surprising how straightforward that purchase was, isn't it? But what is it about human milk that's made it so desirable? We know from population studies that having this milk early in life benefits infants and could affect health later in life too.

Julia - This milk has been honed by millions of years of evolution to provide newborns with a healthy start in life. As well as forging a strong mother-to-baby bond, human milk contains the right balance of nutrients so infants grow at the right rate. And it helps with the development of the immune system and the intestinal microbiome through the transfer of immune factors, as well as bacteria and other bugs.

Chris - But microbes are not the only cells that get transferred during feeding. Cells from the mother also go across and they can take up residents in the baby. Gürkan Öztürk from Istanbul Medipol university has been looking into how and why this happens. What are the cells that go across Gürkan?

Gürkan - They are stem cells. For some time we know that breast milk contains stem cells, but what happens to them in the body of the baby was not known. So in our study, we tracked them to understand at least a part of their story.

Chris - We should be clear, you were looking in animals, but animals are mammals like we are, so we can suggest that the same might be true. But what animals did you look at and how did you follow a cell out of the mother, across the breast, and then into the baby?

Gürkan - The method was quite straightforward. We have special mice who's body cells all produce a green coloured fluorescent molecule called GFP. We took normal mouse pups from a normal mother and had them breastfed by these green fluorescent protein-producing foster mothers. The idea is any cell in the foster mother's milk would be labeled with this green fluorescents. So after pups are fed with this breast milk, we were able to track down GFP-labeled cells in the growing pups at certain intervals with advanced microscopy. And we found them. We confirmed what we observed under microscope with molecular techniques and the breast milk cells were all around the pups bodies.

Chris - Where in the body did they go, these glowing green cells?

Gürkan - Practically, we came across these cells in many parts of the animals, including blood and with the highest amount in the bone marrow. However, our aim was to look at one of the most difficult parts of the body to penetrate -  the brain. Because the brain is normally protected from intrusion with a special barrier. Nevertheless, they were there, and they had differentiated became neurons and support cells, namely glial cells.

Chris - Have you tested out how long these cells persist for? Do we know once they're in the infant, how long they're likely to stay viable for?

Gürkan - In the mouse experiments, we found these cells living up to a year. But this was the maximum time we kept. So it's halfway to their expected life duration actually. So I think, unless there is a host versus graft reaction that is brain tissue rejection reaction, there is no reason why these cells should die. So what's the use of this cells? It's a very interesting question. First of all, besides these stem cells, breast milk also contains immune cells. By giving these immune cells to the baby, it is quite understandable that the baby is supported immunologically by the mother. But stem cells are quite curious because we have some new findings, additional findings in other experiments, that showed that these cells lodge into the bone marrow and somehow they are mobilised to injury sites. In another study we created stroke in the animal and when we inject breast milk stem cells, these cells aggregated in the site of injury and took part in the repair process.

Chris - My final question is one common practice is that if a mum can't use her own milk in a baby - and we see this in our hospital quite often where we've got a baby needs some donor milk - we will go to another mother and get some breast milk from her. If you do get milk from a mum that's not your own, does that make a difference? Do you end up with someone else's mum being part of you?

Gürkan - To me, it sounds like a kind of kinship. You and the other baby who shared your mother's breast milk have the original maternal cells that came from your mother. Very interestingly, in Islam there is a concept of breast milk siblings; any babies who are fed by a mother are considered to be breast milk siblings. They are like sisters and brothers. They cannot even get married to each other. So this is quite a curious case. I think by understanding more and more about these breast milk cells, we will be defining a new kind of kinship, not only in the brain, maybe in other tissues and organs.

Chris - Amazing. And I suppose you could say if you end up with bits of your mum in your brain that's "food for thought", isn't it? Thank you very much, Gürkan Öztürk there

Scientist holding dish of cells in lab

32:49 - Generating human milk in the lab

We might soon be able to create a human milk substitute using breast cells in a dish

Generating human milk in the lab
Michelle Egger, BioMilq

Feeding a baby with human milk is beneficial because it provides the right balance for a baby's nutritional needs. But this is not an option for all parents and many in this situation turn to formula feeds as a substitute. But formulas are not made from human milk, and there are some elements of breast milk that can't be reproduced reliably in formula feeds. But could biotechnology provide us with a solution? The team at BioMilq, a company based in North Carolina, are using cultured breast cells to produce milk in a test tube. Chris Smith spoke to co-founder Michelle Egger…

Michelle - Reaching for the formula tin today is absolutely what most parents are faced with having to do if, if breastfeeding isn't working because of the circumstances in their life. But we think there should be better options for parents and they shouldn't be forced to make trade offs that put their children's nutrition at risk.

Chris - If you do a head-to-head comparison between what's in formula and what's in breast milk, what's the difference?

Michelle - When you take a look at breast milk specifically, there's so many bioactive components that we know help seed the microbiome. They help as a prebiotic, actually support the development of healthy gut microbiome, which I think science still has only really scratched the surface of our understanding of microbiome development. And there's 2,500 plus macro- and micronutrients that are very distinctly human, that we know have an incredibly important outcome on the development of a child.

Chris - Why don't we just put what's missing in the tin?

Michelle - There are a lot of companies trying to do that, frankly, just trying to add back a few things to make formula a little bit closer to human milk. But there is really a lot of structure and function capability that exists in breast milk that we just can't replicate in formula. You're talking about one cell type that produces thousands of components simultaneously.

Chris - So is that how you are seeking to attack the problem then, you're going to the cells armed with that recipe book and saying can we harness the cells?

Michelle - Yes, we like to joke our cells are our employees to some extent - they do the heavy lifting. Human mammary epithelial cells, which are the cell type that lines the mammary gland within the human body, create these layers where they're able to pull in nutrients from one side, turn on their biosynthetic pathways within the layer, and secrete something different out the other side. So in the body, they do this in the mammary gland to pull in nutrients from the mother's blood turn on their biosynthetic pathways and secrete milk into the gland, which is then suckled by a child. We basically do the same thing here at BioMilq, but we utilise a construct and a device, a bioreactor, which enables them to have the same orientation, and we provide the stimulation and the actual nutrients through media instead of through blood, as it would arrive in the mother's body.

Chris - Genius. So this like an in vitro breast, isn't it? In the sense that on one side you've got the goodies coming in akin to like the mother's bloodstream, the cells draw out from that supply whatever they need, and then turn it into what they would naturally do in the breast, which they secrete on the other side, and that's what you are capturing as your surrogate breast milk?

Michelle - Exactly. And a lot of our challenge is really in cracking the code on how these cells produce their best, how they're their most prolific, and then giving them those cues in that environment where they're able to be hyper-lactive and produce as much milk in the highest quality as possible.

Chris - Where did you get the cells from?

Michelle - We have two ways that we derive cells. One is through tissue. So women who undergo breast reduction surgery often will donate their tissue to science, fully informed on how the tissue will be used. And then we can also derive cells from milk. We have really strict bioethical protocols and processes we follow because we think people should know exactly how these cells are going to be utilized now and in the future.

Chris - Obviously the critical question is, is the product any good? Do you get something resembling milk, both visually, but also more importantly, biochemically? Is it really human milk you're making?

Michelle - It's not bioidentical to breast milk. It's not going to be exactly what is produced at the breast, nor is it going to have the contamination that comes through skin-to-skin transfer that's good for a healthy baby gut microbiome. But as we look at omics level analysis, we are producing something that we're quite comfortable calling human milk based on the compositional levels of proteins, lipids, sugars that we would expect to see. To have leaped beyond the idea of maybe we produce a component or two of human milk to producing thousands of the most important macro- and micronutrients of breast milk all at once, we think is a pretty amazing advancement in science. Fundamentally, what we're doing is just harnessing nature but we've never produced a product for infants like this before. We're only likely 18 months or so from a product that could be commercialized, but we have a lot of work to do to make sure we're all in agreement that it should be and is safe to be.

Chris - Fascinating that isn't it? Michelle Egger there talking about her new method for in vitro breast milk production.

Baby being fed with a bottle

37:58 - The importance of human milk banks

Human milk banks provide food to sick babies or parents who cannot produce milk, as well as vital support

The importance of human milk banks
Natalie Shenker, Imperial College London and Human Milk Foundation

Another way parents can get human milk for their babies is using a human milk bank, where donors with a surfeit of milk can make it available for others to use. Natalie Shenker from Imperial College London and director of the Human Milk Foundation explains to Julia Ravey the importance of donor milk and how it is processed. The milk for these banks is treated in a very different way to the delivery Julia received…

Julia - Oh, this must be the milk! Oh my goodness. So the postman must have come into my building and... Oh my goodness. What has been left at my door is a brown envelope with a pouch of liquid inside. I really wanted to speak to the postman, but maybe he knew what was in it and thought I don't want to interact with that person. So let's open it up. I've never felt dread like this opening in a package, if I'm honest. There's a cold pack, which is completely thawed out and, oh, it's a little bit cold, I guess. And then the milk itself is in a fridge bag, like a bag you put food in in the fridge and wrapped in tinfoil. I'm not going to unwrap that because I think I'll leave that to the professionals at the lab. This is the Clinical Microbiology and Public Health laboratory at Addenbrookes hospital in Cambridge that tests milk donated to the milk bank. And these donations are absolutely vital. Natalie Shanker, a research fellow at Imperial College London and co-founder of the Human Milk Foundation, which operates the UK's first charitable non-profit human milk bank, told me about how donated milk is used and also how it is screened.

Natalie - Human milk banks work a lot like the blood transfusion service. So mums will go through a screening process where they are interviewed, they have a questionnaire to fill in, and then they'll go through blood tests, which exclude infectious diseases that can be transmitted through milk. Milk is collected and brought into the milk bank where it's specially heat-treated, pasteurised and it undergoes microbiology testing to make sure that there's no harmful bacteria after that process.

Julia - Why is it now so important that we have these screens in place?

Natalie - The reason that milk banks have always had safety at their very heart is because over the last 40 years, donor human milk has primarily been used to feed very vulnerable, very low birth weight and premature babies, where even the slightest problem could cause a real clinical problem for that baby.

Julia - This milk can go to babies who are quite sick. Does it also go to other family situations? For example, if parents have adopted?

Natalie - Indeed. So we have just celebrated today sending milk to the 400th family that we've supported in our community program. And this is run through our charity, it's all entirely free to the parents. But what we have is a team of lactation consultants and breastfeeding counselors who are able to support breastfeeding journeys as best as possible, but also to provide that donor milk as of bridge. In those situations, we've supported over 60 families where the mother's been diagnosed with cancer and is undergoing cancer therapy, or the parents had bilateral mastectomy. Babies fed that after adoption, after surrogacy. It's giving the choice to the parents, but also enabling that baby to receive human milk for a little bit longer.

Julia - Hello. How are you? I come bearing some milk. Have you ever seen milk come to you like this before?

Lab Technician - No.

Julia - So this is breast milk, which has been bought from eBay...

Lab Technician - Oh right!

Julia - Natalie describes how human milk bought from the internet could cause problems if given to a baby...

Natalie - If that was coming through the post for my baby, I wouldn't be feeding it to my baby. And the reason for that is you've got no idea how that milk has been expressed, what equipment has been used, who's expressed milk and what might be in there. And there's also the problem of milk that isn't refrigerated or frozen quite quickly, not being of the quality that would be best to give to babies. And that's, that's incredibly worrying. Women across the country; if you ask during pregnancy, over 85% want to feed their own babies, but by a week, fewer than half are doing so on the latest data that we have. Now that's not for women not trying, it's for women being absolutely desperate and left to go through some really traumatic times, largely unsupported because there's been no serious investment in this sort of support for decades. Families are desperate and where they have no other option, some will choose to take this rather more risky path. And that's really where the work of the charity is coming in, because we want to make a nationally equitable service. That would mean that there would be an alternative and that we can help work with other third sector organizations and NHS healthcare professionals to make sure that no family has to resort this sort of approach to feed their babies.

Julia - Thank you so much. Bye bye. Bye.

Julia - The shock on her face when I said that this milk had been bought on the internet, never seen a sample quite like that before. So let's see what the results bring on Friday.

Chris - Stay tuned, and we'll tell you towards the end of the program, what turned up.

Scientists looking down a microscope in the lab

44:01 - Using human milk to study breast cancer

Scientists are using breast milk to help better understand one of the biggest killers in the UK

Using human milk to study breast cancer
Alicia-Jane Twigger, University of Cambridge

Donating human milk is really useful for babies and parents who need it, but these donations are also now being used to help us advance science. Specifically, to learn more about breast cancer. Julia Ravey spoke to Alicia-Jane Twigger from the University of Cambridge is doing just that…

Alicia - What we found overall is that women who breastfeed and lactate actually have an overall low risk of breast cancer, but there are some factors that influence that. That could include how old a woman is when she becomes pregnant and lactates, as well as the duration of the breastfeeding experience.

Julia - These studies so far are all correlational. Do we have any ideas about if there could be a mechanism and what that could be?

Alicia - There are actually some animal studies that have looked into this and have found that there seems to be some remnant cells after parity called parity induced cells. There is some evidence to suggest that there are epigenetic changes that occur within the cells. Of course, this has been really difficult to validate in humans because getting human tissue, especially during pregnancy and lactation, is so difficult.

Julia - So how are you using human milk to help us better understand breast cancer risk?

Alicia - So, what we've done as part of our study, is we've centrifuged fresh milk samples, and then we're able to extract the cells, and we've done a whole bunch of different analyses, including growing the cells in culture, examining the protein profile and the transcriptomic or RNA profile, to then see how similar the cells and the breast milk are compared to the cells in the actual breast itself.

Julia - And what have you found in this research so far?

Alicia - So, what we found is that the cells in milk seem to predominantly be either the secretory cells in milk or the immune cell subtypes, and the secretory cells in milk have a very similar profile to luminal progenitor cells in the breast tissue.

Julia - And what do luminal progenitor cells normally do in breast tissue?

Alicia - Evidence from mass studies have found these luminal progenitor cells seem to be the ones that actually then differentiate into the milk secretory cells, but they also seem to be the cell of origin for many aggressive breast cancer subtypes.

Julia - So, if these are being excreted in the milk, drawing lactation, do you think that this could potentially be a mechanism whereby these cells are being reduced in their numbers and this might be some sort of mechanism that is linking breastfeeding and breast cancer?

Alicia - There's two schools of thought as to why cells enter the milk. One reason could be that they somehow have a benefit for the infant, the other might be, as you say, like a clearing mechanism of the metabolically active, almost damaged cells into the milk. And it's the supportive mechanism for mother to clear out these really energy exhausted cells.

Julia - With these studies, you found that, in human milk, there are these cells that look similar to what we have in the breast tissue, and these cells are potentially progenitors for cancerous cells down the line. What's the next step there? We found the cells, now what are we going to look for?

Alicia - Something that I'd like to do in the future is to look at how DNA damaged these cells are and whether there are mutations, and then see if we can use that as a proxy to then measure a women's potential for getting breast cancer. Obviously, the great thing about getting the cells out of the milk is it's not invasive, and we can do this across a really large population.

Julia - And if this was a potential screening mechanism, what would be the case for individuals who do not lactate?

Alicia - That's a good question. I think we would only be able to do this, as I said, in this timeframe for women who are pregnant and lactating, or post-pregnancy during lactation. But hopefully, overall, this will give us a better insight into what's happening in the breast during these changes, and whether there might be strategies to try and encourage damaged cells to either be cleared or for them to be reprogrammed somehow using therapeutic strategies.

Julia - How important has human milk donation been to your research?

Alicia - It's been hugely important, actually. I feel so lucky to be supported by a huge community of women who have donated milk. Historically, I found that women who are donating to breastfeeding research are so interested, they're so supportive, and obviously I couldn't do my work without them.

Julia - It's really interesting to see human milk be used in this way to advance science.

Alicia - Yeah, absolutely. Obviously, this is my passion; this is something that I have found fascinating for a very long time. I'm very grateful to the community for their support in providing samples. I'm really excited to be doing this.

rack of weights at a gym

48:47 - Why some adults are drinking human milk

It's no longer just being used to feed hungry babies

Why some adults are drinking human milk
JJ Ritenour & Sarah Steele, University of Cambridge

Outside the realm of medicine and science, human milk has acquired a new customer base, potentially explaining how Julia was able to so quickly source this fluid online. One of our Naked Scientists, Anoushka Handa, got in touch with JJ Ritenour, a bodybuilder from South Carolina, who has a unique motivation for consuming human milk, and discusses this market with the University of Cambridge's Sarah Steele…

JJ - Everyone's always looking for an edge some way. And I just randomly came across this YouTube video: huge ripped guy, pro bodybuilder, and he was supplementing with his daughter's breast milk. Because I knew we had extra milk in the fridge at the time from when my girlfriend was breastfeeding, and usually the extra stuff she would just dump down the drain, I was like, "Well, instead of binning it, do you care if I put it in my shake?" She was like, "Yeah, sure. I mean, we're just going to throw it away. If you think it's going to help, why not?" I took it from the fridge and just dumped it in my shake and knocked it back.

Anoushka - I saw that you had another person who you used to source the human milk. What was the first step in sourcing that human milk?

JJ - I was concerned, like, "Where am I going to get it from?" Clearly my kids were grown at this point. I did try to research, and I just found that for someone like me walking off the street, "Hey, do you guys have breast milk to donate to me, to use as supplement in my shake?" Everybody was saying no.

Anoushka - Is that from a milk bank?

JJ - Yeah. From the milk bank. I made a random post on one of my friends' Facebook pages, who recently had a baby, about how some people will pay for breast milk. I get a ding, a notification from Tiffany and it's like, "Hey, friend of a friend, I have some breast milk if you're interested?"

Anoushka - And when you got the milk, did you take any precautions before you drank it?

JJ - No, I sure didn't. I just looked at it. It wasn't any crazy colours, I didn't see any pink swirls or anything like that. If I saw something like that, I would assume it was blood in the milk. It looked just like all the other breast milk.

Anoushka - There's a series of things that can be passed down from human milk down to a child. Do you think that you were worried about any infections like HIV, STIs, any bacteria that would be passed to you?

JJ - It didn't cross my mind. I know that through childbirth, those can be transmitted, but I didn't really put much thought into it being in the milk.

Anoushka - Let's take Tiffany out of the equation. She decides to stop giving milk to anyone. If you are presented with two new people, same situation: one which has screened the milk, one, which hasn't, and they're selling it at the same price, who would you go for?

JJ - If it's the same, and the only difference is that it's screened, I definitely would probably go with the screened one. It would be a different conversation. I'm like, "Well, this milk is actually screened and pasteurised against pathogens" and make sure that I'm being as healthy as possible in this space.

Julia - Someone who is concerned about the increased adult interest in human milk is Sarah Steele, a senior research associate at Cambridge Public Health, focusing on problems at the interface of public health and law. Anoushka Handa asked her what problems human milk sales might cause, and why she thinks this market is more in demand.

Sarah - Clinicians, the World Health Organisation, various midwifery and nursing bodies have put out there all this information on human milk, because it's "wonder-food." That's really critical work that they're doing, but people misunderstand it. There's a lot of online forums, a lot of social media posts that misconstrue it and engage in misinformation. Sometimes I'm concerned it's disinformation about the benefits of drinking this for adults.

Anoushka - Are there any benefits to drinking this as an adult and what risks are adults taking by drinking human milk as well?

Sarah - The answer, to be completely honest with you, is there's not enough good science to show what the benefits are of drinking this as an adult. Like any food, it can offer us benefits, but also, like any food, it can pose us risks. This is a body fluid, right? It is at the end of the day something we are producing; it contains white blood cells, it can contain pus, it can contain red blood cells - you name it, it can contain it as a body fluid. Certain things pass across to the milk, like caffeine, or if people are consuming alcohol. So, there's dietary influences and drug influences here. There are a range of things that actually wind up in breast milk that pose risks to consumers. We've seen advertisements where you can buy this milk off of eBay, shipped via Royal Mail second class. I'd be really worried about that safety for an infant consumer, but for adults, the issue for me and the big risk here is for immunocompromised adults, which we're seeing this milk being touted online as a miracle food for.

Anoushka - Are there other people who also buy this milk for various different reasons?

Sarah - So we've seen a lot of posts in body builder forums with gyms. I think one of the big movements I'm seeing a lot of is around clean eating. It's not necessarily terribly cleaner in any sense. What is making me very nervous is, as we move to view this as a clean-eat treat, as a kind of alternative to your whey protein shake, how are you handling it? How are you getting it? Who are you getting it from?

Anoushka - Ethically, should adults be drinking this at all?

Sarah - I think as we move to consume this and see it as a commercial product, or a thing that can be bought and sold, we could wind up in a situation where we engage in deeply troubling and unethical practices. If adult consumers start to see this as a viable alternative to normal milk in supermarkets, how do we get enough of it? We end up with women pumping for profit to become, in effect, human dairy cows. That is a horrifying scenario to me. If adult consumers drink this in vast quantities and see this as the new whey protein shake, we need to ask where the milk comes from and have regulatory oversight to make sure that unethical practices aren't continued.

Chris - Indeed. We're speaking about human milk being sold online. You probably remember earlier on in the program you heard Julia being quite surprised herself, when the sample she had ordered on eBay turned up at her doorstep and the postman hot-footed it before she had a chance to find out how surprised he was. Well, I've got the lab results, Julia, because I took this into our laboratory at the Addenbrooke's hospital in Cambridge and asked them to put this through the protocol that we use in the hospital when a mother donates some breast milk for use in, for instance, our neonatal intensive care unit for a baby whose mum might not be able to breastfeed it. And we have a protocol we follow to test not for viruses under these circumstances, but for bacteria. Now I've kept you in the dark to a certain extent here. What do you think we found?

Julia - I think the plates will be teeming with bacteria because breast milk has bacteria in it anyway. So that's what I'm thinking - lots of growth. What did we see?

Chris - That's exactly what I expected to see because, as you say, our skin is covered in microbes and we know that babies rely on getting those from their mums because it helps to set up their intestinal flora. I was gobsmacked to find that these plates were completely clear. This was sterile. There were no organisms detected at all. The only way I can suggest this is either someone had pasteurised this milk or added something to stop bacteria growing and kill them all off. Or was it even breast milk? We don't actually know. So, I suggest there's scope for another programme in this and you and I have to go away and find out. 

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