The Medical Research Council (MRC) Max Perutz Science Writing Award is open to MRC-funded PhD students who are invited to write about why their area of research is important. This year’s 10 shortlisted topics included immune therapies for cancer, the drug-related death rate in Scotland and the neglected tropical disease schistosomiasis. The high quality of entries made judging difficult. Ultimately, the panel, made up of Ian Tucker from the Observer, Roger Highfield from the Science Museum, journalist Samira Ahmed, science communication professor Andy Ridgeway, Jennifer Anderson from the MRC and award-winning young science writer Zara Hussan, agreed that the £1,500 prize should go to Emily Cornish, PhD candidate at the EGA Institute for Women’s Health, University College London, for her essay on recurrent loss of pregnancy “I am so excited to have won this inspirational award,” says Emily.
The winning essay
Emily Cornish. Photography: Joel Knight
Amy’s third baby was born in the middle of the night. In the split second before crying, everyone in the OR held their breath. He was lurking in a corner with a large ice bucket, waiting to collect the placenta. The stakes felt incredibly high. Both of baby William’s sisters were stillborn due to a placental disorder called chronic histiocytic intervillosis (CHI).
Most obstetricians have never heard of CHI. It is a rare condition that affects one in 2,000 pregnancies and can only be diagnosed after delivery by examining the placenta under a microscope. The aim of my PhD is to discover the cause of this disease.
In a healthy pregnancy, the mother’s blood flows through the placenta in a channel called the intervillous space, where it comes into direct contact with tree-like branching structures known as placental villi. This is where the vital gas and nutrient exchange between mother and baby takes place. In CHI, the channel becomes clogged with maternal immune cells, impairing the exchange process and causing serious consequences for the baby. Only half of these pregnancies result in a live birth and some babies have to be delivered months early by emergency caesarean section to give them a chance of survival.
CHI usually affects women who are well and fit, with no medical problems. It comes out of the blue and has a devastating impact on couples expecting a baby. The cruelest thing about CHI is that eight out of 10 times it will recur in a subsequent pregnancy.
Any miscarriage or stillbirth is emotionally devastating for parents, but for most it is unlikely to happen again. This is where CHI is different. When Amy received the diagnosis after her second daughter died, she experienced a “double grief”—not just the loss of Grace, but the loss of the future and the family she had envisioned. There are no tests that can reliably predict recurrence of CHI, so these subsequent pregnancies require incredibly close follow-up. Many women will have scans every fortnight, struggling to suppress their fear as they return to the same ultrasound departments where their previous losses were diagnosed.
The cause of CHI is unknown. However, when you look at a placenta with CHI through a microscope, at the cellular level, it looks remarkably like a rejected kidney transplant. My hypothesis is that affected mothers make an antibody that attacks the developing placenta. This leads to inflammation of the placenta and an influx of maternal immune cells. Support for this theory comes from the fact that when couples affected by CHI undergo IVF using their own eggs and sperm and transfer the embryo to a surrogate, the pregnancy progresses normally without signs of CHI. This confirms that the problem stems from the mother’s immune system.
Initially, the design of a research study focusing on CHI was daunting: how could I hope to recruit a significant number of women when the disease is so rare? Luckily, I was rescued by a woman named Claudia and a Facebook group.
Clàudia lost four children to CHI in the space of three years. As she navigated the pain of learning to live without her children, she decided to raise the profile of this mysterious and brutal disease. Since then, she has been a tireless advocate for advancing CHI research and helps run a Facebook support group for affected women. The group has over 700 members and is a lifesaver for parents struggling to come to terms with their diagnosis.
Finding a miracle cure is unrealistic, but my vision is to make concrete advances in our understanding of this disease.
Despite its rarity, and thanks to Clàudia’s group, I have managed to recruit more than 30 women to my study. He collects blood and placenta samples to look for unusual immune cells, proteins, or antibodies that might explain what’s going wrong in your pregnancies. I also analyze their DNA to look for variations in their genetic code that may predispose them to CHI.
By purifying antibodies from their blood and comparing them to women who have had healthy, uncomplicated pregnancies, I have shown that women with CHI react abnormally to placental proteins. My next challenge is to determine exactly what triggers this reaction and unravel the molecular basis of how this leads to catastrophic placental damage. And the ultimate goal is to use this knowledge to develop new targeted treatments that can prevent recurrence.
My team is already making progress on the final question. Clàudia lost her children 10 years ago and finally resorted to surrogacy, as nothing her doctors tried to stop the relentless recurrence of CHI. However, in recent months we have become cautiously optimistic about a new treatment protocol that involves suppressing the mother’s immune system during pregnancy. Once again, we drew on the parallels between CHI placentas and rejected transplants. This treatment is the same that people with organ transplants take to prevent their body from rejecting the donated organ. It’s an intensive cocktail of drugs that requires regular blood tests and close monitoring for early signs of potentially dangerous side effects. We’ve only treated a handful of women so far, but most have gone home with a healthy baby.
But until we figure out the cause of CHI, these treatments are, at best, an educated guess. I’m only nine months into my PhD and I’m well aware that finding a miracle cure is an unrealistic dream. However, my vision is to make concrete advances in our understanding of CHI so that future treatments can be tailored to the precise defect in the immune system of affected women.
After Amy lost her daughters, she felt like she’d been “kicked out of the motherhood club.” She couldn’t bear to lose another baby and although the prospect of a heavily medicated pregnancy filled her with anxiety, she decided to take a gamble. Amy took more than 1,000 pills and injected herself with a blood thinner at least 200 times during her pregnancy with William. She traveled to the hospital on commuter trains during the pandemic, came for scans alone due to the restrictive Covid visiting policy and had blood tests almost every week.
I am inspired and humbled by the extraordinary courage and determination of the women who embark on this regime. CHI has been neglected by obstetrical researchers, but thankfully the women who have experienced it are highly motivated and desperate to educate us. If my research can draw attention to the massive impact of CHI and give some hope to affected families, it seems worth spending nights crouched in an operating room with an ice bucket.