In the year 2023, the human cell is on the cutting table at Anatomy Lesson
Rheumatologist Iain McInnes is optimistic about improved rheumatoid arthritis drugs as scientists increasingly understand how human cells communicate with each other. Next Thursday, he will give the annual Anatomy Lesson at a sold-out Concertgebouw. “Like dancers, with cells you have to look not at the individual but at the whole group.”
As a young doctor, British immunologist Iain McInnes saw in a family member what the autoimmune disease rheumatoid arthritis can do. Since then, he has been studying the mechanisms that cause the disease at the cellular level. McInnes has since become a world-renowned scientist in arthritis research. He also founded a platform where pharmaceutical companies turn research results into clinical trials and drugs. Next Thursday, McInnes will be the keynote speaker at the public lecture “The Anatomy Lesson” at the Concertgebouw.
The Anatomy Lesson is an annual medical public lecture at the crossroads of medicine and society organized by Amsterdam UMC and the Volkskrant. The tradition takes place this year for the 30th time and is based on an annual public dissection for laymen in the sixteenth and seventeenth centuries held by the surgeons’ guild. The modern version traditionally includes musical entertainment.
Molecular research is a lot less visible than the anatomy of the human body. Suppose you could get a mega-sized cell on stage, what would you show?
“Funny, because I start my lecture by looking back to the seventeenth century, when the surgeon’s guild in Amsterdam organized a public dissection for a wide audience. If you look at the original painting, The Anatomy Lesson, where an arm is dissected, the surgeons saw the muscles, joints and tissue of the arm. But they didn’t have the ability to understand everything underneath.
“To answer your question: I wouldn’t show one cell, but several. It’s almost like a group of dancers, where you often look not at what one dancer does, but how the group moves together. This is also how it works in rheumatism, where different cells in the immune system collectively attack the joints, causing pain and swelling. Imagine the audience at the Concertgebouw, where most visitors will probably be sitting next to friends, family, or colleagues. What relationships do they have with each other and what conversations are they having? We want to know the same thing about the cells in the human body. Until recently, it was like looking into space and seeing only the vague outline of a galaxy without knowing what planets or stars were there. The technology of the past 20 years has given us much more clarity.”
And what can we do with that knowledge?
“With this we can eliminate proteins in the immune system that cause rheumatism in a much more targeted way. About 25 years ago, rheumatoid arthritis medications shut down much of the immune system. The result was that patients suffered side effects and had an increased risk of infection. With the advent of customized proteins (monoclonal antibodies), we were able to block certain proteins from the immune system very selectively. You could compare it to a surgeon who can suddenly perform surgery with a scalpel instead of a sledgehammer. These drugs, called TNF blockers, were a huge improvement for many patients. The challenge of the last 20 years has been to discover how many more of these molecular targets we could find. We are now at five or six. Quite an advance, the limits of which we are now running into. Indeed, for a new generation of drugs, we need an even better understanding of the detailed conversations going on between cells in tissue. With spatial microscopy, scientists can visualize parts of human cells in 2D, 3D and relative to other cells so we can look even further. Whereas before we could see one to ten proteins (of expressed genes) in one cell, now we can see hundreds or even thousands. That change is like taking a plane from Europe to America instead of a boat.”
Keeping all those proteins apart seems incredibly complex. Isn’t it likely that inaccurate measurements will be made, as Greek-American epidemiologist John Ioannidis pointed out at an earlier “Anatomy Lesson”?
“To my knowledge, there are no scientific methods with no margins of error. The clever scientist anticipates this and tries to answer the same question using as many different methods as possible. If all those methods result in the same answer, then we can begin to think that the answer might be correct. It is true that science is only as good as the scientific methods at the time. Science is constantly changing. We now look at the data from 20 years ago with different eyes. You can see that as a problem or take it into account and remain modest about your results.”
What would you like Amsterdam students to take away from your talk?
“First of all, be curious, since the future belongs to those who ask the best questions. Second, technology can change the world, but only if you ask the right questions. So with good questions and good technology, we can make a huge difference. Not only to rheumatoid arthritis, but also to many other diseases.”
