Today, the name Adolf Friedrich Nolde is virtually unknown, even in the circles of medical historians. A young German professor of medicine and midwifery from the late eighteenth and early nineteenth centuries, this man, while mourned and eulogized at the time of his early death, has been quickly forgotten.

However, Nolde deserves to be remembered, and his work merits closer examination, especially because of his writings in the final years of the eighteenth century and his focus on the development of a scientific foundation for the study of drug treatments and the development of research ethics.

In his treatise, [Reminder of some of the necessary conditions for the critical appraisal of a drug], published in 1799, Nolde defines and enumerates a set of eight rules for the conduct of pharmacological research. In the first seven of these rules, Nolde highlights the need for the study of high-quality and “genuine and unadulterated” drugs that are “prescribed in an appropriate manner.”  It is his eighth rule, however, that merits the closest examination, for here he looks at the issue of research misconduct and the impact it may have on both scientific endeavour and patients’ well-being. He summarizes this rule as follows:

Rule 8. When announcing a new drug or recommending a known drug nothing at all should be omitted about anything that could have an influence on the correct assessment of the drug, and it would be shameful if observations were to be fabricated or distorted at the expense of the truth.”

Nolde justifies the inclusion of such a rule by noting that, “unfortunately one sees many a result which has been recorded untruthfully,” and goes on to state that, “not everything which physicians publish under the promising titles of ‘Observations and Experiences’ can be taken at face value.” What might be seen as very much a twenty-first-century problem appears to have been a well-recognized phenomenon even in the eighteenth century.

He describes instances of fabrication, where results are simply made up and then published, as well as instances of falsification, where results are willfully manipulated to tell a different story. In both, he expresses his concern that, “the public can be deceived in this way.” Moreover, he admonishes those whom he believes have corrupted the scientific literature:

Such actions are of course extremely unworthy of any honourable man and should rightly bring disgrace upon him. Not only does he deceive the reading physicians in this way and shamefully betray the time and effort invested by them with the best of intentions, but he is also sinning against science itself by wilfully corrupting the degree of certainty of which science is capable and acting irresponsibly toward the public who entrust their health and lives to their physicians. Anyone who dares to misrepresent the truth so deliberately should consider carefully the unpredictable consequences of his actions and look to his conscience!”

Nolde asks for a comprehensive approach to scientific reporting, but recognizes that this is a more difficult path:

Whoever has the will and resolve to present really instructive observations to the medical public will undoubtedly have to apply himself much more diligently than one who cares not what he writes to the world.”

He also notes the difficulty this may present to the reader, but rejects the idea that this is an unnecessary burden:

I reject the criticism that the length and detail of such comprehensive reporting would bore and tire the reader. Anyone who, as a critic or a prospective physician seeking guidance, turns to such observations does not do so for amusement as in reading a novel. . . . The physician, if he so wills and has the ability to do so, can report his observations so that they read well and easily despite their necessary thoroughness. It is not the deluge of words or the number of pages that give a report its comprehensiveness, but rather the complete and accurate reporting of everything, which is relevant without falling into the trap of long-winded, tiresome verbosity. As regards the time a physician spends reading such reports of observations he would have much less cause for regret if, in a day, he read two or three well-written reports than if he read hundreds which were of little use.”

He also recognizes the importance of education stating:

. . . it would be very desirable if it were very strongly impressed on young physicians at university that their duty was to remain loyal to the truth in all circumstances and that plying their trade in silence would be preferable to doing so with lies and deceit.”

Nolde concludes:

Only when we know this relationship exactly and that the tests which produced the data were undertaken with all practical care, intelligence, diligence and attention, are we able to obtain the information and the degree of certainty needed in order to judge the value or worthlessness of a drug. Truth is always better than deception and definite certainty preferable to precarious uncertainty.”

Regarding the research misconduct that he recognizes as toxic to scientific endeavour and the practice of medicine, he recommends that it be exposed and expunged:

. . . all corner-cutting, fabrications and deceptions of the ‘literary’ physicians, produced in their thousands, should be treated with the greatest contempt as soon as they are recognized as such and deserve no better than eternal oblivion.”

Working in the late eighteenth century, Nolde was part of the medical and scientific enlightenment that recognized the deficiencies of a past reliant on folklore and anecdotes to inform medical practices. He and many of his contemporaries realized that good practice had to be founded on experience and, furthermore, that that experience should be gathered and reported in a rigorous way.

Writing specifically about the evaluation of new drug therapies, Nolde enumerated a series of key principles or rules that he proposed must be followed for such assessments to be valid. What his rules cover are a number of the key aspects of the scientific method and would be readily recognizable to a modern-day clinical pharmacologist. But, in addition to these principles of practice, Nolde felt the need to emphasize the ethical aspects of research practice and reporting.

Today, we are acutely aware of the importance of research misconduct, and major efforts are being made to expose and root out such practices. We understand how the fabrication and falsification of research data and their publication can fatally undermine modern medicine, but so did Nolde, more than 200 years ago. Not only did he recognize the problem, he also understood the implications of a corrupt scientific literature and its impact on patient care. He also realized that education of junior practitioners and researchers is key to both solving the problem and making the practice completely professionally unacceptable.

Nolde’s contribution is not only of interest for historical curiosity but is also a potent reminder that the challenges of clinical research are not new. The problems we face today are similar to those that troubled the minds of our forebears. We are concerned with the quality of clinical research and its integrity and, at times, even its veracity. If we are looking for solutions, we might do worse than to consider those put forward by thinkers such as Nolde. Recognition of the problem, a public refusal to accept such a state of affairs, and then ensuring that junior staff are properly educated were Nolde’s solutions. These are also increasingly the modern solutions to our problem of misconduct and fraud in scientific research.

© Allan Gaw 2019

 

An earlier version of this article was published with Thomas Demant in International Journal of History and Philosophy of Medicine 2016; 6: 10602 www.ijhpm.org doi: 10.18550/ijhpm.0602

Now available in paperback…

Testing the Waters: Lessons from the History of Drug Research

What can we learn from the past that may be relevant to modern drug research?

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“I cannot recommend it highly enough: even if you read nothing else about the origins of drug research and what it can (should?) teach us, read this….This is a ‘buy’.”  Madhu Davis review in Pharmaceutical Physician May 2016.

My other books currently available on kindle:

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