This is a ground-breaking discovery, right out of science fiction. But when you see him sitting there – talking enthusiastically, gleaming eyes darting here and there under a pair of narrow eyebrows – you’d almost forget that. After years of tinkering, testing and improving, Peter de Keizer and his colleagues have managed to develop a protein that not only stops ageing, but can even partially reverse it.
For the section Science Cowboys, Geert Maarse talks to scientists who go just that bit further than their colleagues. Biologist Peter de Keizer (Erasmus MC, molecular genetics) hit the world headlines with the peptide Proxofim (or FOXO4-DRI) which reverses ageing in mice (paper). Very elderly lab mice got their energy back and thinning fur was restored. More and more people are now also starting to experiment with it.
The substance is called Proxofim. And although wherever he appears (he went to the TV talk show RTL Late Night and TV news magazine Nieuwsuur, for example), the research is clearly described as involving mice and, he is obviously already a couple of steps ahead in his mind. Thinking about treating people.
Can you give us an idea how important this research is?
“For a very long time, we’ve had to resign ourselves to the fact that we get old. We had all kinds of quick fixes which enabled us to tackle symptoms, but we didn’t know the real cause, let alone whether we could do anything about it. Over the past two or three years, research into ageing has gone into overdrive, and this finding is part of that trend. And within a generation, we will seriously start to reap the benefits.”
What does that mean?
“We’ve known for some time that diet restriction – eating less – slows down ageing. Furthermore, stem cell therapy is being developed, although that’s still in the experimental phase. And our research has now shown that you can kill senescent cells, which are like rotten apples which contaminate their surroundings with all sorts of rubbish. When you count up all these individual breakthroughs, you can age more healthily.”
De Keizer starts to talk faster: “It’s a bit like a bike: the less you use it in the rain, the less it wears out. That’s the diet restriction. If a part breaks, you can replace it. That’s stem cell therapy. What we’ve now discovered is a substance that removes rust.”
You’re very enthusiastic about this?
“Yes, it makes me very happy.”
Are things going fast enough for you?
“I’m young and healthy, so I’ve got time. But my inbox is full of messages from people who are old, or terminally ill. That puts quite a lot of pressure on us researchers, although I do find it hugely motivating.”
How often do you get emails like that?
“Every week. If we’ve been highlighted in the media somewhere, you immediately get a response. We get messages from patients or relatives. Often people with cancer. But also people who want me to help their sick cat or dog. This morning I received an email from someone asking if she could use it on her horse.”
How do you manage that?
“Unfortunately, we have to take a very business-like and legal approach. However bad a person’s situation, and sometimes these are people in their thirties who are out of treatment options, I can’t give them anything. If anything goes wrong, we are liable. That’s a cowardly answer, but it’s the reality.”
I can understand someone wanting to test it. On themselves, their brother or mother. Why can’t they?
“If you put a substance on the market without clearly analysing how it works and what the side effects are, all sorts of things could go wrong. In France last year, people actually died because a painkiller was launched on the market too soon. Lots of substances ultimately prove too toxic for people.”
But that doesn’t really matter if you’ve only got a few months to live?
“No, you’re right. That’s why I’ve embarked on a kind of crusade to get the law changed. If you’re ill, you don’t want to wait ten years. When the rules for clinical translation were drawn up around thirty years ago, the Internet didn’t exist. A substance like ours is very easy to make. We now order it from a company in Lelystad, where other people can go as well. Anyone who is a bit useful with Google could get it home the day after tomorrow (via this Chinese company, for example, GM). And then you can use it on yourself.”
You have two children. Imagine one of them gets an incurable disease which could be treated with this substance. Would you do it?
“It really depends on the disease. I don’t think so. But there’s nothing much you can do if people use it anyway. They take stranger things already.”
A man in the United States, who wasn’t even ill, took it. What do you think of that?
“Somehow it’s fantastic that he claims he saw the same effects as we found with mice. And that it didn’t make him ill. If it goes wrong, because he takes too much or injects in the wrong place, we have a problem. Then the correct translation to the clinic will suffer a huge delay.”
But if it goes well…
“…it’s self reporting and that doesn’t tell you anything. At least, that’s how many people see it.”
In around ten years’ time, we’ll know more about how Proxofim works. Then you can either throw it in the bin or you get a Nobel Prize.
“The bin is always a possibility!”
It’s still not exactly certain how it can help people. What do you think?
“It affects hair loss, we could use it for that. And we have reason to believe that the peptide can affect glioblastomas, very aggressive brain tumours. These are patients for whom chemoradiotherapy and surgery are no longer an option. People who only have six months to live. Hopefully, we could do something for them in the clinic. I don’t think that curing cancer is possible. But you might make it chronic. You can see that in prostate cancer, for example. Thanks to all kinds of treatments, lots of men live for thirty years with it and die from something else.”
How long will that take?
“You have to be very careful with that. It may be three years before we can start clinical trials, so test on people. We first have to do the preclinical toxicology studies with different types of animal. And then make sure that we can produce the substance with a purity of 99.9 percent. But believe me, I hope that we’ll get there sooner.”
This research has been reported all over the world, among colleagues, but also in the popular media. Do you like that?
“I want to show that lots of amazing things are happening in the field of ageing research and I want to be an ambassador for the field. And it gives me energy. In the lab, we did a little dance when we discovered that it worked. We’ve still got that feeling and we want to communicate that. It can help put the research on the map, in politics, for example.”
And there are also researchers who say: that’s not for me.
“I couldn’t care less. There are even people who feel that you shouldn’t interfere with ageing, because it’s God’s will or because it’s just part of life. Or they feel that researchers should keep well away from practice, and be as ‘pure’ and fundamental as possible. I was like that before I went to America. But there I got caught up in the Silicon Valley mentality. I worked alongside a retired millionaire who was totally focused on ageing research. He didn’t have a thyroid and every time I made a great discovery, he’d ask: when will you be doing the clinical trials? I’d then think: leave me alone, I’m a researcher. Until I saw more and more people having real impact with their work. In the Netherlands, people really look down on entrepreneurship. Academia and industry should never go together, otherwise you’re corrupt. So we give our research away to American companies. I feel: if you’ve discovered something, take it to people yourself. So we set up our own company, with investors, and we’re going to organise the trial with the help of the best doctors in Rotterdam. Use industry to take your discovery back to society. That’s why we do it, isn’t it?”
