Dr. Corina Beerli, specialist area Research Management and Operations Research, competence sector Science and Technology and Dr. Matthias Wittwer, head of the Proteomics, Bioinformatics and Toxins Group, Spiez Laboratory

Natural occurrence and application of toxins

In nature, toxins are widespread and primarily serve animals and plants to ward off predators. But even micro-organisms such as bacteria unfurl their pathogenic effect by forming highly-effective toxins. The bacterial nerve poison botulinum neurotoxin is thus the most poisonous substance known to date. Just one millionth of a gram causes severe muscle paralysis which leads to death in humans. Nevertheless, the neurotoxin is used in minute amounts under the trade name Botox in aesthetic medicine. The most frequent common cause of toxin poisoning is the consumption of food contaminated with bacteria. The safety of food is monitored by the cantonal laboratories and national reference centres, as some toxins are so extraordinarily poisonous. Infections with toxin-forming bacteria must also be reported to the authorities.

Toxins as bioweapons

With regard to internal security, certain toxins are held on international lists of substances which are subject to strict export controls and the dissemination of which as a bioweapon should be prevented. In particular, the herbicide ricin and the shellfish toxin saxitoxin have a high bioterrorist potential. The Organisation for the Prohibition of Chemical Weapons (OPCW) holds these two toxins on the list of those substances which are classified as particularly dangerous. They are thus subject to the regulations of the Chemical Weapons Convention, in the same way as other highly potent warfare agents such as sarin or mustard gas. However, in contrast to chemical warfare agents, toxins have not yet ever been used in armed conflicts on a large scale, despite the extensive bioweapon programmes of some states. Nevertheless, toxins represent a means of terror for selective use, as they are easily available. This applies in particular for ricin, as it remains as a concentrated poison in press residue when castor oil is manufactured.

In the thwarted terror attack in Cologne in 2018, 3150 castor beans and 84 milligrams of ricin were seized in the apartment of an Islamist, in addition to equipment for an explosive device. According to an expert opinion, this quantity would have been sufficient to kill more than ten thousand people. In America too, letters laced with ricin have been sent to high-ranking politicians over the last 20 years, including to ex-President Barack Obama. Due to these incidents, the use of toxins for a bioterrorist attack is estimated as more probable than the use of viruses or bacteria.

Toxin analysis in the Spiez Laboratory

The specialised service Biology at the Spiez Laboratory deals with the protection of biological threats such as pathogens of dangerous diseases and toxins. On the one hand, the Laboratory researches how these pathogens and toxins trigger diseases and how they spread. On the other hand, the focus is on verifying and characterising them. The Spiez Laboratory offers this analysis for a selected range of pathogens and toxins for clinical samples as well as samples from the environment. In order to uniquely identify what are known as biological agents such as bacteria, viruses or parasites according to international standards, several methods are basically necessary, each of which examine different characteristics. In the case of toxins, this is performed as follows: In the first step, employees isolate the substance by means of biochemical procedures from the sample and identify the substance through highly-sensitive analytical procedures. They then examine whether the toxin is still biologically active, in other words, functional. For this purpose, they use cell cultures to test whether the toxin has harmful effects on the cells. Finally, they characterise the structure of the toxin with mass spectrometry, a procedure to determine the mass of atoms or molecules. The quality of these analytical methods is periodically tested in international ring trials, in which various research institutes within Europe simultaneously receive an unknown toxin sample for analysis. The Spiez Laboratory always performs very well and is one of the leading research institutes in this field.

Automation in an emergency

Up to now, the Spiez Laboratory has been analysing toxins especially on a small scale and with highly-specialised experts. However, as the COVID-19 crisis has now shown, a large number of samples need to be processed in an emergency. At the same time, it is a major challenge to maintain the process and the quality of the toxin analysis over a longer period of time and to avoid errors. This is precisely where the research project supported by armasuisse Science and Technology

“Next Generation Toxin Detection” comes in. The aim of this project is to automate processing of the samples as much as possible and to standardise toxin analysis. For this purpose, the Spiez Laboratory first of all acquired, thanks to the support and expertise of armasuisse employees, an analysis device which can process almost a hundred samples simultaneously. Secondly, it is currently introducing an information system for the Laboratory which maps the entire analytical process and enables the samples to be monitored from the point where they are received until the test reports are compiled. Depending on the toxin, the selected analysis methods can differ and therefore need to be optimised for each toxin. In the first step, the Spiez Laboratory now establishes the workflow for the bioterrorist-relevant toxins ricin and botulinum neurotoxin. The automated analysis of small-molecular toxins such as saxitoxin is then carried out in a further step. The highly-standardised and automated analysis methods enable members of the Armed Forces to be trained in refresher courses. In the event of an emergency, the Spiez Laboratory is thus prepared to start up toxin analysis through support by the NBC troops within a short time as well as to guarantee a high throughput of samples over a longer period of time. This joint research project between the Spiez Laboratory and armasuisse Science and Technology can thus be considered a success.