Digital chronotherapeutics
The biggest technological leap in medicine since the invention of the kymograph will be the modern smartphone’s ability to easily access acquired data on body and lifestyle parameters. Once the data is acquired it can be assimilated into a computational model of possible health and disease states. A therapeutic feedback control can then be applied, depending on the state, while the health process is continuously monitored.
This data assimilation procedure is described in every modern control engineering handbook. Today it is the method by which an airplane can land on autopilot without any input from the pilot. Tomorrow data assimilation will be the method by which a person’s disease will be treated without a physician. While it looks similar, data assimilation is fundamentally different from neural networks that help autonomous cars learn to drive. In contrast to data assimilation, neural networks are for data mining tasks, i.e., putting data before theory.
Data assimilation systems are putting theory before data, i.e., physiology before smartphone data. A priori knowledge on the physiology is the essential constraint that does not limit but enriches the therapeutics. A priori knowledge on the physiology is a form of a digital mode of action that leads to a new area of digital chronotherapeutics for which continuous monitoring is needed.
Observing health and illness over the course of time
The Kymograph (wave writer) was the first device that could allow a physiological process to be represented in real-time. It drew blood pressure as a curve on endless paper wrapped on a revolving drum. The blood pressure is represented in a Cartesian coordinate system. Cartesian coordinates provide the most convenient way of using mathematics for further analysis of the data. Today, the revolutionary character of this device is not easy to recognize. To monitor physiological processes by curves over time is a concept so pervasively established that we hardly think about it anymore.
Without the kymograph there would be no physiology today. How a physiological process can be transformed into a function of measured values was so vividly demonstrated with the invention of the kymograph that Uwe Heinemann stated that the device “freed physiology from the grips of anatomy” — thus the birth of physiology as an independent discipline.
Similarly, smartphone technology will be the birth of digital chronotherapeutics as a truly independent medical discipline. What is needed now to make smartphone technology more effective as it becomes integrated into day-to-day health monitoring is a better understanding of the relationship between slow biorhythms and states of health and disease. The significance of slow biorhythms can be vividly demonstrated by the story of how Dr. Hobart A. Reinmann met his wife.
How Dr. Hobart A. Reimann met his wife
The history of so-called “periodic diseases” begins with the story of how Dr. Reimann met his wife. On November 4th, 1927, a patient came to see Dr. Reimann. Her right knee was significantly swollen. Dr. Reimann began to measure the circumference of her swollen knee. He also measured the circumference of the left knee as a reference
Nearly 6 cm difference, this must have been clearly visible even without measuring it. Dr. Reimann ordered his patient to see him again the next day, and the day after that. For 141 consecutive days, until March 23rd of the following year, Dr. Reimann measured the circumference of both his patient’s knees.
Why did Dr. Reimann make such an effort to closely monitor his patient’s condition? One answer is simple: Dr. Reimann later married his patient. This explains his continued interest in her knees well enough. The not so simple answer is that Dr. Reimann discovered his first case of a group of medical conditions, which he would study for the rest of his life. 41 years later he termed this group “periodic diseases”.
Young women were known to have knee joints with certain regular effusions. Already in 1845, the clinical literature described such a case. Dr. Reimann’s stunning observation was something special. Within the 20 weeks, he observed 19 periodical swellings of the right knee and its subsiding to normal in about a week. On the left side were also 19 swellings and their subsiding. The effusions of his patient’s knee joints were not only periodical but also right and left knee had a phase shift of exactly 180°, i.e., when the right side was swollen the left side was not, and vice versa.
In 1968, Dr. Reimann published his little-known paper entitled “Periodic Diseases” (written in German, although Reiman was working in the US, at the Hahnemann Medical College and Hospital in Philadelphia). In this paper, he described a group of 10 periodic diseases each of unknown cause, i.e., idiopathic diseases. He pointed out that only a total of 2,000 cases had been described in the clinical literature. The very first case was a periodic peritonitis, described in the 17th century. Another case was his patient and wife with her intermittent hydrarthrosis.
Today, the most prevalent example is migraine with one billion cases worldwide. Migraine is actually a so-called »dynamic disease« not merely a »periodic disease«, a subtle difference that goes beyond the scope of this essay. In essence, a dynamic disease provides the means to develop digital mode of action to treat or even cure the disease, while “periodic disease” merely a descriptive term is.
The story of how Dr. Hobart A. Reinmann met his wife, also illustrates the differences between “primary” and “secondary” uses of health data. This differentiation in usage helps to explain why it is taking longer than necessary to establish health monitoring smartphone technologies. However, in light of current events, the development of these technologies will probably happen faster, because the pandemic will increase social acceptance of continuous health monitoring.
Insights delivered through digital health will become indispensable
All data safety concerns aside, if the primary use case delivers what it promises, namely insights into an individual’s health that improves care and outcomes, smartphone technology will become indispensable to increasing the value of health care.
Think about the excitement in the neurological world in 1924 when Hans Berger recorded the first human electroencephalography (EEG) and discovered the alpha wave rhythm. Like the kymograph, the EEG is a device to observe a physiological process in terms of waves. His work was followed by many other discoveries of EEG frequency bands and their connection to health and disease. The EEG soon became indispensable for diagnosing and monitoring many neurological diseases. Moreover, the EEG is also used today as a therapeutic tool in neurofeedback.
Now we have reason to as excited as they were in 1924. With today’s smartphone technology we will detect bodily rhythms driven by very slow biological clocks with periods ranging from days to weeks, months, and years. In other words, we will uncover many more periodical diseases amenable to chronotherapeutics by the design of digital mode of actions using data assimilation methods.
While Dr. Reimann’s work took an enormous effort, this is something that will soon become an effortless part of our everyday life: to monitor our health every day.
