Publication Analysis 2005-2011
by Kathleen Gransalke, Labtimes 01/2015
Toxicological research has turned from the study of naturally occurring toxins to man-made contaminants, effecting our health and ecosystems. Highly cited toxicology labs are found all over Europe, with hot spots in Edinburgh and Stockholm.
“Guilty” said the man in the back, “He’s guilty and must die,” yelled another. The executioner, knowing, nodded his head and crushed the hemlock leaves to prepare the convict’s final drink. As the toxic liquid flowed through his body, his feet became numb, then his legs – but he was still wide awake. When the poison reached his diaphragm, he stopped breathing and died a peaceful but tragic death.
Poison hemlock (Conium maculatum) is one of the most toxic plants in Europe (besides the wolf’s bane, Aconitum napellus). Its most potent toxin, coniine, binds to nicotinic acetylcholine receptors of the peripheral nervous system, causing ascending muscular paralysis. In ancient Greece, it was served as a death cocktail to damned delinquents – just like philosopher Socrates. Having toxicological knowledge, however, was not only advantageous in old-fashioned jurisdiction; more recently toxins have also helped to unravel basic biological relations. The insecticide rotenone, for instance, was used to elucidate the workings of the respiratory chain in mitochondria and 19th century French physiologist, Claude Bernard, studied the neuromuscular junction with the arrow poison, curare. Speaking of bows and arrows, the world ‘toxicology’ is derived from the ancient Greek word τόξον (tókson), meaning bow.
Modern toxicologists are, however, a little bit less interested in naturally occurring toxic substances. Many of them focus more on man-made compounds with as yet unknown effects on health and ecosystems, as we shall see later.
First, let’s have a look at European countries’ performance in toxicology-themed research. As we haven’t yet figured out a way to filter out toxicological papers from multidisciplinary journals, the numbers for total citations, articles and the citation-per-article ratio are based on specialist journals like Aquatic Toxicology, Nanotoxicology or Toxicological Sciences only. For the most-cited authors in toxicology, we decided not to discriminate between specialist and non-specialist journals.
No surprise at the top of the nations’ performance list: England and Germany are the top two countries, far ahead of France and Italy in third and fourth place. Turkey scored a good 12th place but another country pushed itself to the fore even more. Despite just about missing the top 20, Slovakia is the undisputed number one when it comes to citations-per-article (30.3). Not even Scotland (28.1) and Switzerland (26.0) were able to keep up. The global comparison revealed one more surprise. Whereas in other disciplines they are usually way behind their US colleagues, here, European toxicologists received more citations per article than their US peers, or from any of the analysed countries, for that matter.
Now, we have arrived at toxicology’s hottest papers, published between 2005 and 2011. Interestingly, four of the top five papers are about cytotoxicity. How does basic cell biology relate to toxicology? In 2006, Sten Orrenius and Boris Zhivatovsky from the Karolinska Institute in Stockholm rhetorically asked: Does it matter how cells die? Their prompt answer: “Yes, for our understanding of chemical hazards and the mechanisms by which toxicants can damage our cells and tissues, it certainly does! Cell death is the ultimate result of toxicity, and elucidating the signalling pathways involved is highly relevant for our understanding of the cellular targets and mechanisms of action of chemical toxins.”
With their cellular toxicology approach, Orrenius (16th) and Zhivatovsky (4th) also secured themselves a spot in the top 30 toxicologists in Europe. Once again, it wasn’t easy to separate the ‘toxic’ wheat from the ‘non-toxic’ chaff. A most important criterion for inclusion was the number of papers in toxicology specialist journals. To epidemiologists, we paid special attention and decided on a case-by-case basis.
Considering the researchers’ home affiliations, all four corners of Europe are well-represented in our top 30. North (Sweden, Denmark), East (Czech Republic), South (Spain, Italy, Portugal) and West (England, Belgium, Germany, Scotland, Austria, the Netherlands) – toxicology is an important research discipline almost everywhere in Europe. But there are ‘toxic clusters’: the University of Edinburgh (fielding three researchers) is one and the Karolinska Institute in Stockholm (fielding four) another. Among our top 30 are also three women.
The dangers from eating poisonous plants seem to be more or less eliminated but that doesn’t mean we are safe from toxic harm. On the contrary, we, or our bodies, now have to deal with modern poisons in the air, our food, drinking water, clothes and homes. The majority of our top 30 toxicologists, thus, monitors or studies health effects of exposure to toxic substances, such as nanoparticles and nanomaterials (Vicki Stone, 5th; Rodger Duffin, 10th; Steffen Loft, 12th; Richard Handy, 22nd), metals, like cadmium, mercury and lead (Josep Domingo, 6th; Marie Vahter, 14th), flame retardants used in furniture, for instance, (Adrian Covaci, 2nd; Åke Bergman, 19th), pesticides (Jürgen Angerer, 8th) and endocrine disruptors (Colin Janssen, 28th).
Environmental pollutants do not only affect human health. Wildlife, particularly aquatic wildlife, has to cope with a mélange of unnatural and toxic compounds in their habitat. Ecotoxicologists like Ronny Blust (11th), Charles Tyler (15th) and Amadeu Soares (29th) want to understand whether or how these chemicals interfere with the physiological and or developmental processes of fish, water fleas and sea snails.
Not to forget the clinical toxicologists, who study the safety of drugs. B. Kevin Park (9th), for instance, looks into drug-induced liver injury and drug-induced cutaneous toxicity. Hans Maurer (25th) experiments with designer drugs and their toxicity.
And finally, we come to the usual ‘outliers’, including our number one, Mark Cronin from the University of Liverpool. He approaches toxicology in the in silico way, predicting the toxicity of industrial chemicals, pharmaceuticals, cosmetics and food additives. Currently, he coordinates the EU COSMOS project – Integrated In Silico Models for the Prediction of Human Repeated Dose Toxicity of COSMetics to Optimise Safety. The project’s main aim is to “develop freely available tools and workflows to predict the safety to humans following the use of cosmetic ingredients”. At the moment, the COSMOS database comprises more than 12,000 toxicity studies for more than 1,600 compounds.
Rudolf Krska (20th) is set apart from the majority of the other top 30 researchers by studying naturally occurring toxins, viz. mycotoxins. In his lab in Tulln an der Donau, he works on methods to detect mycotoxins in food and feed.
As we have learnt during our current publication analysis, toxicology also grapples with a well-known problem – reproducibility of research data. In a recent editorial in Particle and Fibre Toxicology, Rodger Duffin and colleagues from Edinburgh and The Netherlands, write: “The issue of reproducibility of results in toxicology has long been a concern and, perhaps, at the back of many of our minds but not necessarily at the forefront of our thinking. Are the results we have published literally our results or are they reproducible and truly part of a credible theory?”
In particular, Duffin et al. point out the importance of accurate method description as “even minor modifications of conventional in vitro toxicity assays (e.g. due to sample handling/preparation issues) can have an important impact on study reproducibility”. Hence, Duffin and co. suggest five ‘practical points’ every particle toxicologist should take to heart:
- Be specific. If it’s graphene, then is it actually graphene, i.e. a monolayer, or is it few-layer graphene, or graphite platelets?
- Characterise, characterise, characterise. Characterise in relation to your hypothesis or research question.
- Use statistics to question your results rather than simply confirming a theory.
- Write your hypothesis in advance of running the experiment. If your theory is robust it should survive your best efforts to challenge it.
- Take a ‘belts and braces’ approach to confirming findings. Use multiple approaches, doses, time points, replicates and controls. You don’t want to be caught with your trousers down.
This advice surely applies not only to toxicology but to all biological disciplines.
View the Picture: Most Cited Authors
Last Changed: 04.02.2015