Kramme is using technology developed at the Wyss Institute to enable people to have children on their own terms
By Lindsay Brownell
Every day, members of the Wyss community reimagine a world where anything is possible. It’s a world of scientific discovery, imagination, and innovation, where diseases are cured, climate change is reversed, pandemics are prevented, and lives are changed for the better. The ideas that we are bringing to life through our research and engineering might seem like science fiction today, but we’re working on turning them into reality.
Christian Kramme is a former Wyss Institute researcher who is now the VP of Cell Engineering at a women’s health startup called Gameto. We sat down with him to learn more about how he, and the company, are reimagining a world without infertility.
This interview has been edited for length and clarity
Christian Kramme: If I could reimagine the world, I think about true reproductive autonomy. I think about a world in which when a person wants to have a child, that’s possible, and it’s on their time frame. I think it’s a beautiful world. Infertility is a huge global phenomenon and it’s getting worse. I think so often about that, really, the fertility solutions on the table are hard, they’re expensive, and there’s not a lot of equity there, not a lot of the people who actually want to have children can have children due to biology, but also due to cost.
I think about a world in which when a person wants to have a child, that’s possible, and it’s on their time frame. I think it’s a beautiful world.
Lindsay Brownell: How did you decide to focus your research on creating a new solution to infertility?
Christian: When I came to Harvard, I knew really that I wanted to be a cell engineer, and I’d always been interested in this idea of working with cells and changing cell fates, and being able to engineer stem cells at will. And I was really, really interested in infertility. My brother struggled with infertility in my family, and so I know how important fertility and family making can be in a person’s life. And so, the only challenge, the only thing George [Church] asks in the Church Lab is that you think big. And so when we sat down, it was just like, ‘What could be one of the biggest applications of cell engineering?’ And it would be to make an egg. To truly recapitulate a gamete being developed outside the body. It is a huge space to have incredible impact in both the short-term and long-term. So it was kind of a match for me in my mind.
Lindsay: So, as you embarked on this journey to try to engineer an egg outside the human body, what did you discover?
Christian: In around 2019, early parts of 2020, it became very apparent to us and really in the literature and the field, that one of the most important things that you need for this process of allowing a gamete to develop is the support cell. Gametes are almost unable to do nearly anything themselves – they require this very coordinated support environment to regulate their metabolism and have their growth factors and develop. And so we were really, really interested in not only directly generating gametes, but also the support environment. And this is where the original idea [came from] of trying to build organoid models that are basically ovaries in a dish and they could be something like a gamete production factory.
Lindsay: Tell me about Gameto – how did the company get involved in this effort?
Christian: A lot of this work was funded originally and still is today by Gameto. And Gameto was really involved with the Wyss, very early on, with a sponsored research agreement, and we had a choice pretty early on: what can Gameto do to find a need and fill that need with the technology available? And we see it in IVF.
Lindsay: Why does IVF represent such a big unmet need? More than a million babies have been born via IVF in the US, so clearly it works.
Christian: IVF in general today, I mean, it’s a great system, it’s a beautiful treatment, obviously, for fertility. But it doesn’t work as well as a lot of us like to think it does, and it’s extremely expensive and it’s extremely burdensome on women. It requires an insane amount of gonadotropins and stimulants. And the whole point, the whole idea of the process is to essentially use a woman’s ovaries as an incubator and try to get as much of the hormone stimulants in there as you possibly can to mature as many eggs in vivo as possible, extract them with a needle, any of those eggs that are mature, you can use them – any of the eggs that are immature, you throw them away. And to us, that’s a great first step, but what we knew is that the point of support cells is to mature eggs, is to help germ cells develop and mature. And we now know that we can very readily make these support cells from stem cells. And so, we had the idea early on of, “Well, what if we could build an ovary in a dish?” Take out a lot of that burden that the woman needs to go through, don’t mature the eggs very much in vivo, pull them out early, very little gonadotropin stimulation, put them in a dish and mature them by putting them in the support cell environment?
And, we’re certainly not the first to think of the concept of in vitro maturation (it’s been around actually longer than IVF), but we’re definitely the first who is able to take stem cells, make ovarian support cells, and use those to mature [gametes]. And we’re seeing great success.
We had the idea early on of, ‘Well, what if we could build an ovary in a dish?’
Lindsay: That’s amazing. What’s the current status of Gameto’s work with this technology?
Christian: We actually work with clinics around the world and we’re in preclinical testing right now to actually take immature eggs from IVF and from recruited donors, mature them in vivo, and be able to make great mature eggs that fertilize and form embryos. That’s really what we want to do, is try to close that gap [to] make IVF actually a) more affordable, but [also] b) more accessible.
Every single year, more people are becoming infertile and the solutions have to get bigger and bolder, and more accessible. And so, that’s what I see is the kind of world of the future, and where I want to be.
Lindsay: Thank you for joining us and stay tuned for more stories about how the Wyss Institute is reimagining the world.
