Emeritus professor Lex van der Eb (1934) and his wife Titia are sitting at their kitchen table in Oegstgeest. They’ve known each other since 1954, when they met while studying biology. A painting on the wall shows Van der Eb wearing a toga. It is the twin of a painting in the Academy Building, but that one is ‘more serious’, according to Titia. ‘This one looks more like Lex like you would find him in the supermarket – even though I won’t allow him to go there until there’s a corona vaccine.’
Despite the temporary isolation, it is one of his own discoveries that might make a corona vaccine possible. The research Van der Eb conducted in the 1970s laid the foundations for many of the current therapies against viruses. His name has been mentioned in the same sentence as the words Nobel Prize, but he is quick to brush off any rumors.
His choice to study biology was easily made: ‘I didn’t want to handle patients, so no medicine.’ But the interest for viruses only came later and somewhat by chance, when he was conscripted into the military after he finished his degree. Rather boldly, the young biologist he approached an officer to ask if there were any research places available. ‘That colonel reacted rather gruffly when an upstart like me approached him directly. But it turned out he did have a place to work on a smallpox vaccine in Leiden. That was the beginning of my contact with viruses. Without that officer, I probably wouldn’t have come across them.’
After his conscription, PhD and postdoc (at Caltech, Pasadena), Van der Eb started his own research group in Leiden. Not long before that, scientists had discovered that some adenoviruses, a relatively harmless pathogen to humans, were able to turn rat cells into tumor cells. Van der Eb knew what he wanted to research: to see if it was possible to create a tumor cell using only viral DNA.
It was the early days of DNA research and scientists were rushing to discover all the possibilities of the hereditary molecule. Titia: ‘I remember your research group grew at a huge pace. The first year it was just six of us round a table at a party. The next year the whole house was full.’
One of the new group members was the Canadian postdoc Frank Graham. ‘I had tried to get viral DNA working in an animal cell quite number of times’, Van der Eb says. ‘Frank started by repeating all my experiments, without success. He then spent a year trying all known techniques on rat cells, again to no avail.’
The duo was about to give up when Graham decided to try one last thing: adding calcium chloride. The idea wasn’t a complete guess, calcium was already being used to get bacteria to absorb DNA. Adding that specific compound turned out to be the answer to the problem they had been working on for more than a year. Van der Eb: ‘It was a stroke of luck. Who would’ve thought of adding calcium?’
The new technique suddenly made it possible too adapt animal cells using viral DNA. The first experiments using rat cells went swimmingly, but altering human tissue took considerably longer. Still, the duo succeeded. They created the immortal cell HEK-293. HEK, short for Human Embryonic Kidney, denotes the source of the cells used. 293 is the number of the final successful experiment and alludes to the number of attempts that were necessary to create the cell line.
Every time human cells multiply, the lose a tiny bit of DNA from the ends of their genome. After a number of cell divisions, the DNA is too heavily damaged and the cells dies. But thanks to the inserted adenovirus DNA, the HEK-293 act like tumor cells that don’t have fraying DNA. The result is a cell that can multiply infinitely many times.
After decades, HEK-293 is still one of the most used cells in the pharmaceutical industry. Regeneron, the medicine American president Trump used against Covid was produced using Van der Ebs immoral cells. Regeneron is not undisputed in the United States, however. Conservative Americans are unhappy the original cells used to create HEK-239 were derived from an aborted fetus.
Making medicines and vaccines was never his aim, Van der Eb admits. ‘The idea that we could use immortal cells to produce vaccines only came much later. I just wanted to do fundamental research. I’m glad I had the time and freedom to do just that.’
Titia concurs: ‘Nowadays people want an immediate answers to their questions. And it has to make money.’ Van der Eb: ‘Most of what you discover will advance science, but is worthless outside of that. Discoveries like the calcium technique are rare. Broad, fundamental research is the source of major breakthroughs.’
In 1995, Van der Eb was approached by a former PhD candidate, Dinko Valerio. Was he interested in making an improved version of HEK-293, more suited for clinical applications? The time was ripe to make a new immortal cell with major commercial potential, Valerio thought.
The partnership resulted in the PER.C6 cell (‘Primary Embryonic Retina Clone 6’), immortal , just like its predecessor, but made from retinal cells. And moreover: it was safer to use, more efficient, and easier to adapt. PER.C6 can be grown in huge 10,000 liter vats, allowing for large scale production of vaccine components. All in all: the ideal workhorse for the pharmaceutical industry.
And also a potential goldmine, according to the American pharmaceutical giant Johnson & Johnson. In 2011 they acquired over Janssen Vaccins, that had previously taken over Valerio’s company Crucell. The sale meant the PER.C6 cells were now in American hands.
The current corona crisis has brought the sale to the public attention again. Should the Dutch state have stopped Crucell being sold to keep control of vaccine production? The 7.8 million vaccines the government has ordered will now be produced by an American corporation instead of a National Institute for Vaccines. A dear mistake, according to some, but Van der Eb doesn’t seem to be worried. He trusts ‘his’ PER.C6 cells will be able to produce enough vaccines for the entire world, whether they’re growing in the US or the Netherlands.
Ebola, Zika and Influenza
And what about that Nobel Prize? It’s not hard to understand why, as the creator of two cells that form the backbone of vaccine production, his name is mentioned as a possible laureate. ‘Everyone is so focused on Covid’, the biologist answers stoically. ‘Dozens of labs are working on a vaccine, some of them using PER.C6. If Crucell and Johnson & Johnson succeed in creating a safe and functioning vaccine, then you can judge the merit of our work.’
Still, his cells have saved countless live. In the past they’ve been used to make vaccines for ebola, the zika virus en influenza.
Almost as if he doesn’t want to receive any credit, Van der Eb shows a framed drawing, a retirement gift. The drawing is made up of more than a hundred circles, each bearing a name and a photograph of a former colleague, together forming the outline of an adenovirus. PhD candidates, postdocs, analysts and students, images in colour and black-and-white. Together they make up a silent witness to the joint effort of years of research.
Van der Eb himself doesn’t feel any urge to create a corona vaccine himself. He’d rather go camping with Titia, as soon as it is possible again. Scotland is high on their list. A couple of rucksacks hang next to the adenovirus drawing. Ready to go at the first sign of a working corona virus.