The gene-editing engineer working to boost expertise in China

Luhan Yang is the chief executive of Qihan Biotech in Hangzhou, China, which aims to produce the first pig organs that can be successfully transplanted into humans. She also aims to foster innovative biomedical research in her home country. She tells Nature about her career spent between the United States and China, how her business has had to pivot, and her stance on the ethics of gene editing.

Tell me about your current work.

In 2017, I returned to China to found a new biotech company. I wanted to expand on the research I’d been doing at eGenesis, a company I co-founded with geneticist George Church, in Cambridge, Massachusetts, two years before.

I was excited by the idea of bringing the research I’d been doing in the United States to China. We use CRISPR gene-editing technology to modify pig organs for use in human transplants, a process known as xenotransplantation, as well as to modify cells for use in cancer immunotherapy. I felt that combining the resources of both countries could push the boundaries of our research and the gene-editing field itself.

Nature Spotlight: Biomedical engineering in China

When people think about innovative Chinese companies, they think about Alibaba, Tencent or ByteDance: Internet companies that are synonymous with e-commerce and social media.

But I believe that China has the talent pool to do more than produce apps like TikTok.

When I was at university in China, career paths in the biomedical industry were quite limited — the industry hadn’t taken off yet. Now, we have these kinds of company, but they’re quite small. That inspired me to create Qihan to be the powerhouse of gene editing in the biotechnology domain.

How was the move to China?

Moving back to China was like having reverse culture shock. I had never actually worked here before. I grew up in Sichuan province, studied for my undergraduate degree in Beijing, and moved to Harvard Medical School in Cambridge, Massachusetts, to start my PhD in human biology and translational medicine in 2008.

There were things that were completely unfamiliar. For example, in the United States, the eGenesis management team had decades of experience behind it. In China, the management talent pool is still at an earlier stage, so I found myself taking on a lot of different responsibilities.

That said, the absence of institutional norms that dictate how a company is set up has also been an opportunity. In the United States, corporate structures are well established and there’s little room to innovate in how you organize your company. In China, there’s more flexibility to test different company styles and models, which has helped me find ways to be more efficient in how we make progress.

How has your research progressed?

In 2018, a highly contagious viral disease called African swine fever (ASF) spread to China. It wiped out the country’s pig population and, with it, the animals we needed to conduct our xenotransplantation experiments.

To put it into perspective, before ASF, we produced 400 piglets each year for organ-transplantation experiments. To reach this number, we need thousands of female pigs of a specific age. From each pig ovary, we extract ten eggs that are then engineered to become embryos. These are genetically modified and implanted into surrogate mothers. And for any surrogate mother, you need to implant 200–400 embryos to have a chance of producing a viable pig.

It’s not a very efficient process. Many embryos will not survive the initial stages, and those that do might not make it through pregnancy, or the piglets might not live long once they are born. So we need a lot of pigs.

The ASF virus disrupted our whole chain and we largely had to pivot our research focus until we could ensure its predictability again.

What are you focusing on now?

We are working on using CRISPR to produce off-the-shelf cell therapies for blood cancers. At present, cell therapies are customized to individuals and are very expensive. This process involves collecting cells from a patient’s blood, modifying them to recognize and attack cancer cells, and transfusing them back into the body. This can cost as much as US$500,000 per dose for one person.

At Qihan, we are looking at allogeneic cell therapies that use cells from a donor instead of from the patient. These cells, which have already been genetically modified to attack cancer cells, can simply be taken from the freezer and administered to the patient. The whole process is faster, scalable and vastly less expensive.

To make this off-the-shelf product, we need to solve two problems. One is production: to lower costs, we’d need to make a lot of consistent product. We also need to solve the problem of rejection. Because the cells are derived from a donor, it’s likely the patient’s immune system will attempt to destroy the cells. To prevent rejection, we perform genome modifications on donor stem cells to reduce the recipient’s immune response.

Our experience in genome editing and transplantation immunology, gained from years of xenotransplantation research, is really applicable to the cell-therapy products we are developing: it’s the same problem of rejection we’re trying to solve in both cases.

What are the challenges of being a young entrepreneur?

I guess in the Internet industry, people are used to working with very young entrepreneurs. But when it comes to medicine, experience matters. Yes, people have questioned whether I have the background to do things properly and really deliver. And in all honesty, I haven’t actually delivered any medicine or medical interventions yet. However, I am so excited and humble to be a part of this journey.

There are many factors I need to juggle in my job. I need to understand the regulatory environment in different countries, consider the ramifications of geopolitical tension, and reflect on the ethical issues surrounding gene-editing technology, and how to communicate our scientific position to the public.

It did not take me long in my career to realize I did not have all the answers.

Instead, I’ve sought out others who are much more experienced and knowledgeable than I am. I’m now fortunate to have mentors all over the world, many of whom I call friends. I also regularly speak to advisers who are the best in their field, and am blessed to have a talented team of scientists and engineers at Qihan.

A good thing about being young is that you worry a lot less about asking people for help and losing face.

Have you ever experienced a profound setback in your work?

Of course. Doing science is not a sprint, it’s a marathon. Most of the time you face a lot of failure and uncertainty, especially at the beginning of your career.

Many people do not know this, but I almost did not graduate from Harvard, because I failed my qualification examination. The major problem was my poor English — some of my professors had difficulty in understanding me.

Growing up in a small, remote town in China, I did not have a lot of opportunities to practise English. In high school, I was selected to take part in the China National Biology Olympiad. This was a huge honour, but meant that I had to spend most of my time learning about biology and less time focusing on other core subjects, such as English.

So I failed my qualification exam, and I was asked to take English classes for a year to stay at Harvard. I was also not allowed to spend extra time in the laboratory until my English improved. Fortunately, George Church intervened on my behalf. He told the other professors that he could understand what I was trying to communicate, and instead of having me take language classes, he said he would help me practise English.

The other professors agreed, and every week from then on, throughout my PhD and during my time as a postdoc, George would talk with me about science, culture and many other topics. He rebuilt my confidence and taught me how to truly be a great mentor and leader.

How do you feel about the ethical concerns around xenotransplantation?

I think, regardless of your religion and cultural background, most people will agree that protecting human life is one of the highest moral standards we have. Currently, there are more than 100,000 people in the United States in need of a new organ, for example, and many of those will die before one becomes available. If we are able to ensure the safety and feasibility of xenotransplantation, it has the potential to become a life-saving procedure for hundreds of thousands of people across the globe.

I do understand, however, that there are animal-rights concerns. In China, we produce around 600 million pigs for meat every year. For me, ethically, if one pig could potentially have its organs used to save multiple people instead, I think this is something worth exploring.