Why this German is immune to ricin
January 12, 2018
It only takes a few milligrams of ricin to kill you.
When inhaled, injected or ingested, the compound will inhibit the body's capability to synthesize proteins, resulting in failures of the central nervous system, kidneys, liver and other organs.
Death by circulatory shock or organ failure typically occurs within a few days. So far, no clinically-tested antidote exists. And what makes matters even worse: ricin is quite easy to come by as it can be isolated from the seeds of the castor oil plant.
Ricin has been classified as a bioweapon, and has been used several times in murder or terrorist attack attempts.
One famous case was the assassination of Bulgarian dissident writer Georgi Markov. He was killed on Waterloo Bridge in London in 1978 when, allegedly, a passerby touched him with the tip of an umbrella, injecting a ricin pellet into his leg.
The legend of the umbrella murder was born.
But there are a few people who would have survived the attack — and one of them is a patient at University Hospital Münster in western Germany.
A very special patient
Hospital staff call him Jakob: He is 20 years old and has been treated at the hospital since he was born preterm in 1997.
"There was always something wrong with his health," Jakob's mother told German press agency dpa.
Jakob had to have several surgeries and was suffering from a fever.
"We just couldn't understand where this fever came from," said Jakob's doctor Thorsten Marquardt, head of the department for inherited metabolic diseases at University Hospital Münster.
The doctors finally figured it out: Jakob has a genetic defect which prevents him from metabolizing the sugar fucose.
"We know of only two other people in the world with the same defect," Marquardt said, adding that both of them live in Israel.
A void in a sugar molecule called fucose renders their cells immune against ricin — just like Jakob's cells.
Why a lack in sugars makes people immune
Once inside the human body, ricin binds to sugar molecules which are attached all over our body cells' surfaces.
As long as the poison stays outside the cells, everything is fine.
"It becomes a problem as soon as ricin binds to receptors, which constantly turn over between the outside and the inside of a cell," Johannes Stadlmann, researcher at the Institute for Molecular Biotechnology at the Austrian Academy of Sciences in Vienna, told DW. "With the receptors' help, ricin gets transported into the cells."
There, ricin has access to all the cells' vital machinery and starts blocking the synthesis of essential building blocks.
Stadlmann and his colleagues discovered that the sugar fucose changes the appearance of receptors in such a way that ricin can bind to them easily.
The more fucose there is, the more poisonous ricin becomes.
Switching immunity on and off
The Vienna researchers learned of Jakob's condition and asked Thorsten Marquardt in Münster to send over some samples of Jakob's skin.
It all fit together.
"His cell surfaces don't contain any fucose at all," Stadtmann told DW. "That's why he is immune to ricin."
His metabolic defect has taken his toll on Jacob, though. When the doctors finally realized what was wrong with him, his natural development was already irreparably impaired — he has problems walking and speaking. Nowadays, he receives a fucose supplement, providing him with the sugar his body urgently needs.
According to his doctors, the treatment improved his quality of life, but as Stadlmann points out, it also has a side effect: As long as he receives the treatment, ricin once again becomes poisonous for him.
Temporarily immune
In mice experiments, Stadlmann and his team revealed that they can induce ricin immunity. When they injected mice with a fucose inhibitor, the animals became temporarily immune.
Stadlmann points out that it was quite hard to get approval for this kind of animal experiment, though.
"In the end, we were only allowed to feed the animals a very small ricin dosage," he said — just enough to see an affect on the animals without killing them.
The results clearly showed that animals — and probably humans as well — can be rendered immune against ricin with a simple injection. But it only works as a prophylactic. Once someone has ingested or inhaled the poison, it's too late.
The researchers hope that their work will also help with the development of an antidote.
From lab to reality
Stadlmann has never met Jakob in person but he remembers the day when he first saw the boy's picture which Marquardt had sent him.
"This photo really touched my heart," the sugar researcher said.
Seeing the patient that actually had to live with a condition that Stadlmann helped to analyze in the lab was a special moment.
"It was beautiful to see that all this was connected to sugar molecules," he said. "And it is great that in the end this knowledge could actually help a patient."