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Professor Fadil Hannan
Director, Larsson-Rosenquist Foundation Oxford Centre for the Endocrinology of Human Lactation (LRF OCEHL), University of Oxford
Why is it important to build a holistic understanding of how hormones regulate human milk production?
It strikes me as being unusual that although we’re in the 21st century and know a lot about the biology of the human body, very little is understood about how the human mammary gland functions to make milk. It’s really surprising.
If you take the dairy industry, there’s a lot known about how cows make milk, it’s of real commercial importance. But in terms of understanding how breastfeeding women produce milk for their infants, this is a large knowledge gap. Our center is trying to address this gap, particularly given that breastfeeding is of huge importance and benefit, both to maternal health and to the health of the developing baby.
It’s been known for about 100 years that lactation is driven by hormones. The work that has been done to date has been largely using rodent models. We want to advance knowledge for humans, for breastfeeding women. So the goal of our center is to address two topics: first, to understand which hormones are involved in producing milk and secondly, to understand their mechanism of action. The reason why this knowledge is so important is because of the potential benefits for women who have problems with their milk supplies – lactation insufficiency.
As a physician-scientist, you see first-hand the negative impact of lactation insufficiency on mothers and infants. How are you working to address this challenge?
Lactation insufficiency covers a broad range of problems. There are mums who have perceived problems with their milk supply, but there is also a large proportion of women who have genuine biological issues. One of those has to do with the onset of lactation, which occurs within the first two to three days after childbirth. If the onset of lactation is delayed, that’s a major cause of early breastfeeding cessation and breastfeeding failure. We’re working to address this by understanding which hormones trigger the onset of lactation within the first few days after childbirth and characterize how hormones initiate this.
In Oxford we’ve set up an observational clinical study (INSIGHT). We recruit women right at the end of pregnancy who are intending to breastfeed, who have normal healthy term pregnancies, and then we follow them up during the first four days after they’ve given birth. We collect blood, colostrum and milk samples daily during these first four days and assess how hormones change in these samples.
But we also really want to uncover the biology of how mammary cells switch on milk production, so we isolate living mammary cells (from colostrum and breastmilk) and we study their biology. This involves looking at how different components of the cells, called organelles, change during the onset of lactation and undertaking studies to assess the expression and function of key proteins in those cells. What we’re trying to develop is a holistic picture of the biological and hormonal drivers of the onset of lactation.
Your core aims include developing tools to diagnose and treat lactation insufficiency. Could these be adapted for scale up in different regions?
From our clinical work, we hope to develop a set of normative standards for hormones triggering the onset of lactation. For example, if a mother has a delayed onset of lactation, what I’d really like to see implemented in real world clinical practice is a simple biomarker blood test which could indicate if any of her major lactation hormones are abnormally low or abnormally high.
Having a simple blood test to assess the panel of lactation hormones would be a real advance for clinical and rational management of women with lactation problems, and it’s definitely got the scope to be scaled up or used in a range of settings. Whether that’s in low-income settings, the UK or the European Union, a simple hormonal blood test could have valuable applications.
Another aim with our work of studying mammary cell biology in humans relates to identifying which proteins switch on lactation. It will be wonderful to develop a biomarker, let’s say of a protein which is specific to the human mammary cell, that we could measure to tell us whether lactation has been switched on successfully. Being able to utilize hormones and other biomarkers to assess women with lactation problems would be an immense step forward.
Another point relates to therapeutic strategies. The interesting thing about hormones is they are amenable to interventions which could either involve pharmacological treatments or involve treatments without any drugs. For example, prolactin levels are important for triggering milk production, and exercise has been shown to promote prolactin production. It could be that a simple intervention like regular moderate exercise for breastfeeding women could help optimize their milk supply.
There are investigative diagnostic tools as well as therapeutic strategies like exercise which could make an impact and improve maternal well-being in a range of geographical settings.
How can drawing on the resources of an independent research center at Oxford catalyze this relatively new topic in the research landscape and further enable your clinical and research aims?
There have been a few main benefits. The first is that our center is embedded within the hospital maternity unit. We’re able to directly recruit pregnant women and new mothers into our clinical studies. I just have to walk upstairs to our antenatal ultrasound department, and we can meet women who are delighted to help in our studies. So the location has been incredibly important.
The other point about having a research center which is dedicated to advancing knowledge about human lactation is that nothing like this previously existed anywhere in the UK. Once we started getting the center up, establishing a website, it was remarkable how many people approached me with interest. Women who’ve had long standing problems with their breastfeeding and also professionals who help breastfeeding women, whether that’s lactation consultants or doctors, have approached me for advice and also to offer to help with our studies. So, having an independent research center has really acted as a beacon to bring together breastfeeding women and professionals to help us achieve our strategic research goals.
One thing we focus on in our center is to involve individuals with a different mix of skills and abilities, which has been critical to the success of our research. We have physician-scientists like myself, basic scientists, a midwife, and people who’ve never done any research, but who are experts at providing maternity support and also breastfeeding support.
For example, when we recruit new mothers into our studies, they may have recently given birth, and in return for us collecting colostrum or blood to measure their hormones, we offer the new mums breastfeeding support. After we’ve taken a sample, they’ll often say, “that's been incredibly helpful, would you mind coming to see me again tomorrow, and check on my breastfeeding?” What we’re able to provide in our research center directly benefits the participants in our studies.
We’ve also found that some women participating in our study become very passionate about promoting our research. They tell their friends who may also be breastfeeding. They publicize the work that we do in breastfeeding support groups and in the broader community. It’s interesting how news of the work that we do spreads into the Oxfordshire community, which is great to me.
How is the entrepreneurial approach of the Foundation linked to building the LRF OCEHL for long term sustainable impact?
We’re very fortunate that the Foundation has a long-term vision and a plan for helping its centers to succeed, that’s critical. When I first started in this position in Oxford in 2019, we had no track record in our department of doing research into lactation. It takes time to put in place all of the foundations to develop the program of basic science and clinical research. The funding model that the Foundation initially provided, of a five-year center establishment grant, has been paramount to our success.
We can broadly categorize research into two areas: incremental research which gradually advances the field and research which is more high risk, but has the potential benefit of making big gains in advancing the field.
With the endowment funding from the Foundation, we have a chance to pursue research which is of a higher risk, but could really pay out in terms of big, long-term gains in advancing knowledge about human lactation. The entrepreneurial approach imparted by Katharina (Lichtner) has helped me to think about how we use the funding to prioritize high risk research as well as considering how to obtain external grant income for incremental gains in scientific knowledge.
Most grant bodies give you the funds and then you’re left on your own for the duration of that grant. The Foundation is very different, we benefit a lot from the knowledge and expertise that the Foundation can provide in terms of how to maximize the return from the investment, in terms of scientific return. That's really been helpful to me in setting up the Oxford center.
Extending from that, does your engagement with other LRF Center directors help in terms of sharing experiences or best practices?
Some of the other centers are quite new and they’re also in that process of development. I look at the University of California San Diego center set up by Lars Bode. (Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence or LRF MOMI CORE.) That’s more established, and it’s been wonderful to see how he has maximized the financial return from the funding that he’s had and the models that he’s utilized to develop his center into the Human Milk Institute. The progress and the approach that Lars has undertaken has been a helpful model for all of the newer centers as to what we could go on to achieve in the next few years.
Is there anything that you wish to add?
One is to reiterate that our center has really benefited from the two-way interaction with the Foundation. I really value the input from the Foundation in terms of thinking about how to best utilize the funds that we get.
Also, we’re in a really special situation, we are currently setting up a functioning global network of LRF Research Centers dedicated to lactation and breastfeeding. I’m very excited about the future in terms of how we synergize, what we do to achieve a multifaceted understanding about breastfeeding and lactation that spans the basic science arena all of the way through to implementing knowledge to actually helping women with breastfeeding.