Avoiding Phantoms through Research and Teaching in Measurement Science
By Dr. C.J. Easley
Over about sixteen years (1993 – 2008), European authorities were searching for a mysterious woman linked to six murders and more than forty crimes overall. Her DNA was present at every crime scene. Police in Germany even offered a €300,000 reward for information leading to her arrest. This brutal serial killer became known as “the most dangerous woman in Germany,” along with more colorful monikers such as the "woman without a face" or the "Phantom of Heilbronn.” Fortunately, this woman was eventually located, and the mystery was solved.
As a measurement scientist and analytical chemistry professor, my brain first veers off into numbers and unit conversions, of course. Using Google’s favorite euros-to-dollars converter, it appears that €300,000 (euros) today would equal $326,663. Digging a little deeper, inflation rates would make €300,000 in 2008 equal to €369,491 today, and that would put the reward at just over $400,000 in the current market. So, who got the reward worth about $400,000? No one. The woman with the now famous DNA sequence was innocent, and there was never any serial killer.
This investigative blunder was eventually traced to a contamination issue, aided by repeated failures of laboratory personnel who simply did not think to do the appropriate control experiment. The control experiment is often called the “blank” measurement, at least in all the cool analytical chemistry crowds. A quick look through the textbook on my desk reveals that “Blanks account for interference by other species in the sample...” For example, if there happened to be a woman working in a cotton swab factory in Bavaria, and she was not particularly careful with her DNA, and—stay with me—these cotton swabs were used to analyze DNA evidence in just over forty crimes (at least) in Germany without analyzing the cotton swab alone (the blank or control), authorities may misinterpret this meaningless DNA interference and wrongly conclude that there is a lawless, dangerous woman involved in every one of these crimes.
The year the Phantom of Heilbronn mystery was solved, 2008, is the same year that I started my independent research and teaching career here at Auburn’s Department of Chemistry and Biochemistry. My teaching assignments cover chemistry from the fundamental undergraduate level up to the special-topics graduate level where we focus on bioanalytical techniques, and I spend a great deal of my time at the interface between teaching and scholarly research. Thirteen graduate students have completed their Ph.D. degrees under my mentorship, publishing their work in a variety of journal articles. Today there are nine additional researchers working on their dissertations, alongside one more postdoctoral scientist. About thirty different undergraduate students have also worked in our analytical research laboratories since 2008.
Figure: Example image of a microfluidic device used in our research. The channels are about one tenth of a millimeter wide, similar to the diameter of a human hair. Nanoliter volumes, a few billionths of a liter, can be manipulated with high precision.
As I mentioned before, all of us in the Easley Laboratory can be classified as measurement scientists, or more specifically bioanalytical chemists. I can assure you that we run control experiments! We focus mainly on developing tools and methods for scientists and clinicians to use in the future, methods that are carefully designed to minimize measurement interferences or contamination in samples. Our approaches are useful for DNA analysis, but we focus mainly on measurement of various other biomarkers like proteins or small molecules that can predict human disease. In work funded by both the National Institutes of Health (NIH) and National Science Foundation (NSF), we have developed tiny analytical devices using microfluidics and 3D printers, and we also have devised sensors based on electrochemistry, akin to glucose meters used by diabetics. The microdevices have helped us improve the basic understanding of how fat and other tissues respond to nutrients and hormones over short time scales (a few seconds), which could help others develop therapeutics for debilitating conditions like diabetes, obesity, and metabolic syndrome. We focused the customized electrochemical sensors on real-world applications in clinical biosensing for disease monitoring, resulting in a number of patents issued to me and the graduate students. The company that has licensed the technology is looking to use the sensors to make a more immediate impact on human health.
The Phantom of Heilbronn debacle is an extreme example of how the slow relaxing of measurement standards could give grossly misleading results. A false positive cancer diagnosis—or worse, a false negative—is a more meaningful example that unfortunately happens more often. To avoid such costly misinterpretations, it is important that we develop better technology, while at the same time we diligently train the next generation of measurement scientists. By unifying teaching and research, as many of my faculty colleagues do in the College of Sciences and Mathematics (COSAM) and other colleges at Auburn University, we can be confident that the next generation can avoid these types of mistakes in the future. These folks will be practiced at their unit conversion math, and they will do the appropriate control experiments. Not only that, we can make a lasting impact by developing new and improved technology along the way.
Christopher J. Easley, Ph.D. is currently the C. Harry Knowles Professor and Graduate Program Officer (GPO) of Chemistry and Biochemistry at Auburn University. He is an Associate Editor at Analytical Methods (Royal Society of Chemistry) and a board member of the Boshell Diabetes and Metabolic Diseases Research Program at Auburn. He is also a Scientific Advisor for Innamed, Inc. and holds several U.S. patents based on biosensing and microfluidics. Recently, he was awarded the 2019 Mid-Career Achievement Award by the AES Electrophoresis Society and the 2020 COSAM Dean’s Research Award at Auburn.
1. European News. (2009, March 28). 'DNA bungle' haunts German police. BBC News. http://news.bbc.co.uk/2/hi/europe/7966641.stm
2. Parker, M. (2020). Humble pi: when math goes wrong in the real world. Riverhead Books.
3. Wikipedia. (2022, January 9). Phantom of Heilbronn. https://en.wikipedia.org/wiki/Phantom_of_Heilbronn
4. Harris, D. C. (2016). Quantitative Chemical Analysis. 9th ed. W. H. Freeman & Company.