As a physician and clinical researcher engaged in the development of new therapies for kidney disease, I often ask myself, “Can doctors ever know everything about an illness that would enable them to prescribe a treatment that could achieve perfect restoration of normal function?” When the question is phrased in this way, I realize that I have strayed outside the comfortable boundaries of medicine and entered the realm of philosophical inquiry.
The medical question is a variant on an ancient epistemological theme, namely the limits of human cognition. This was a favorite topic in rationalist medieval and early modern philosophy. Two outstanding Jewish philosophers who bracketed this period, Maimonides in the twelfth century and Spinoza in the seventeenth century, came to a very similar understanding of what constituted the highest achievement in human knowledge. They adopted, as Steven Nadler makes clear, a naturalistic view of God and saw divine omnipotence and omniscience expressed in the daily workings of nature. Under quotidian circumstances, nature represents a nexus of innumerable causes and effects linked harmoniously to one another, in accord with the blueprint of the cosmos. The result is the necessary universe that we observe when we look out on the world around us. Spinoza completely denied the possibility of miracles and Maimonides consistently downplayed their role.
Instead, they emphasized the stability of the eternal laws that are hardwired into nature. Spinoza and Maimonides did have fundamental disagreements, which explain why Spinoza was formally banished from the Amsterdam community in 1656. The universe, for Spinoza, was not created, has no purpose, and is not perfect in any normative sense. In sharp contrast, Maimonides saw nature as a reflection of God’s will and, thus, inherently good. They differed sharply in their willingness to allow a purposeful God to intervene in nature under specific discrete circumstances in the service of vital human ethical and political exigencies. For Spinoza, this was a metaphysical impossibility, while for Maimonides an engaged God was essential for the act of creation and for maintenance of a moral responsibility.
However, despite the dramatic differences between these two figures in their conception of a volitional God and his place in workings of the world, they converged on a similar position regarding how nature functions and the human capacity to know the inner workings of the world in which we live. In the Spinozist and Maimonidean systems, the highest knowledge that a rational man/woman can achieve is to perceive and comprehend the immense web of cause and effect in nature and appreciate the perfection of the overall arrangement of things.
Unlike the Platonic notion of the ideal forms which suggests that true knowledge is unattainable to mortal man, both Jewish philosophers held out hope that an understanding of nature can be achieved if the full causal nexus is discovered. A person who truly appreciates all of the interlocking, mutual connections between the countless events occurring at each moment in time will have achieved a genuine understanding of nature and why things are the way they are. For both thinkers, this is as near as man can approach God.
How far did Maimonides and Spinoza take their picture of human knowledge? In the Ethics, Spinoza describes this intellectual process of acquiring full knowledge and developing an appreciation for the necessity of things being the way they are in all their deterministic force. He concludes that this state creates inner psychological tranquility and represents the closest that a man/woman can come to God. He does not back away from this goal and posits that this knowledge will lead to a life of happiness, equanimity, and peace.
Maimonides adopts a more restrained view. He never revised his definition of the highest form of human knowledge. However, in a “skeptical” reading of the Guide of the Perplexed, Maimonides is said to have concluded that man can never fully comprehend the workings of God. Because man/woman is composed of physical matter, he/she is shielded from acquiring the scientific knowledge that could yield demonstrative proofs about the existence and workings of a simple, non-corporeal divine entity. Maimonides was led to conclude that, while a person should strive for this ultimate knowledge, he/she can only appreciate the divine attributes as they manifest themselves through God’s actions in the world. Man/woman has to satisfy him/herself with leading a life of kindness, charity, and justice in imitation of the attributes of God rather than striving for a complete understanding of how things have come to be as they are and how they will unfold in the future.
Returning to medicine, every medical epoch is defined by an illustration that captures the prevailing zeitgeist that animates clinical research. In the aftermath of World War II, a period of explosive growth in technology and biomedical science, laboratories almost invariably had a detailed picture of the Krebs cycle surrounded by many ancillary biochemical pathways prominently hanging on one of their walls. Over the next 20 years, as immunology made impressive advances, the Jerne diagram, which displayed the numerous interactions between the components of the innate and acquired immune systems, replaced the static image of biological reactions on laboratory blackboards. Finally, in the last 10 years, building on the close integration of genomics, proteomics, and metabolomics, a new icon has emerged, the systems biology diagram. They are familiar to everyone who reads contemporary medical research journals. These graphics are characterized by points of various size and print intensity, reflecting their relative importance. The individual nodes are connected to one another by a dense network of crisscrossing lines that reflect the intricate relational web of pathways and interactions between different cellular processes and activities in the context of health or a specific disease state. The adjacent figure is an example and illustrates the network of signaling pathways in the kidney.
Systems biology figures may not be such a graphic innovation. The diagram below, which summarizes the divine forces that animate the cosmos according to one Kabbalistic conception of the sefirot, resembles a simpler version of a systems biology illustration.
Regardless of the vintage of systems biology diagrams, Edward Tufte has made everyone acutely aware of how important a well-conceived graphic can be in conveying vital information. On one level, the transformation in medical science diagrams represents a progression in which biology is initially viewed as a linear sequence of reactions (Krebs cycle), then as a grid of events with multiple causes (Jerne diagram), and finally as a global network of mutually interacting processes. Systems biology has emerged as an alternative to more simplistic, billiard-ball accounts of causality within organisms, in which it is necessary only to understand a very limited set of interactions. Instead, in order to treat a disease, one must appreciate that people who are ill are comprised of a grid of interacting systems that that are constantly changing.
Do the systems biology figures reveal anything about our perception of illness and our capacity to intervene as physicians? These two-dimensional visual display tools of cell function represent an attempt to capture the full complexity of organisms by highlighting the numerous links between different aspects of normal physiology such as metabolism, proliferation, migration, inflammation, and cytoskeletal structure. They are ever-evolving and, as scientific knowledge accumulates, they will become increasingly dense and intricate. It is only a matter of time, with broader access to 3D printers, that these systems biology diagrams will literally leap off the page of journal articles as the lattice of connections between processes is defined more comprehensively and with greater refinement in real time and space.
I suggest that there is a deeper message embedded in these graphic figures and that implicit in these complex illustrations is a philosophical conception of how well doctors can understand health and disease. A profound statement is being made, much more than the simple assertion that life is complex. There is an underlying supposition that since the body is finite it should be fully knowable. The implicit meaning of these systems biology diagrams is that when clinicians perceive and map the entire causal nexus of biological activities within the normal cell and the alterations that are provoked by disease states, then they will be in possession of the true wisdom that is required to know when, where, and how to intervene in a rational manner in order to return the cell, the organ, the patient to good health. Systems biology diagrams cannot provide guidance on questions about whether to treat a patient. But, the presumption is that they will offer up answers to what is the most rational therapy for a given condition.
If systems biology diagrams represent an attempt to understand the disease and its treatment, the question that is begging to be asked is—do the web-like visualizations jive with human psychology and the limits of man’s intellect? Do they foster a realistic expectation of what can be known about illness and what can be done to treat it? Do they promote the design of viable healthcare systems?
Turning to the philosophers, how would Spinoza and Maimonides weigh in on systems biology diagrams? The picture that emerges from these two philosophers is eerily close to what the scientific figures are trying to convey with their increasingly complex depictions of cellular behavior in health and disease. I am not certain about Spinoza, but I speculate that he would have embraced them as a way of imagining the full scope of nature’s laws. He would have viewed them as supporting his efforts to demystify the character of illness and to encourage human efforts to replicate the divine wisdom that balances the myriad causes and effects within the cell when they are perturbed by illness. In contrast, I think Maimonides would have been less sanguine. I imagine that his vast experience as a physician, with his years of service to the Ottoman sultan and the people in his Egyptian community, would have impressed upon him the inability of medical science to fully account for the innumerable processes within the body, environmental interactions, and the consequences of therapeutic interventions. In his medical writings, Maimonides frequently confided that he felt overwhelmed in his medical ministrations and acknowledged the limitations of his remedies.
I find myself inclined to accept Maimonides‘ position. I strongly support the incredibly sophisticated work being conducted in basic science research laboratories to understand the workings of the body in health and disease and I would not ease up on the support for this effort. I share the optimism that this research will improve the treatment of many clinical conditions. However, I share a sense of humility that we are unlikely to ever come up with definitive solutions for most of the health problems that plague people around the world. State-of-the-art research into the mechanism of disease constantly reinforces the complexity of interactions between causative factors, the overlap and tight interaction between signaling cascades and effector systems. The forces acting on patients change over time, the impact of perturbations are modulated by intrinsic features within each individual, and imperfect human beings are prone to perform unpredictable and irrational acts. Any medical attempt to rectify a disturbance in one aspect of the organism and restore healthful harmony inevitably leads to counterbalancing causes and unanticipated effects that may undermine the putative benefit of the treatment.
What then is the medical counterpart to Maimonides’ retreat from perfect knowledge to his recommendation to live an ethical life that imitates the divine attributes? Physicians will always be confronted with the need to intervene effectively and compassionately in the face of acute and chronic disease. However, I propose that clinical wisdom in the Maimonidean sense, one that mirrors a life of kindness, charity, and justice, rests in renewed efforts at preventive medicine. Medical activity to avoid illness by educating people about nutrition, promoting healthy lifestyles, and providing equitable access to care on a global scale may be the human reflection of a well-ordered nature. Implementing successful preventive medicine interventions will still require an understanding of how cells, tissues, organs, and people function in an integrated manner. However, achieving these objectives may be a more feasible objective than aspiring to total understanding of systems biology, health, and disease. This reflects our shared mission as physicians to keep people as healthy as they can be. It does not eliminate but only sidesteps the immodest goal of striving for complete knowledge and perfect interventions to restore the causal nexus of things to their harmonious pre-morbid state of well-being.
In conclusion, philosophers and doctors have struggled with the limits of human knowledge. Listening to philosophers will not make you feel better. But their words may modulate expectations of cure. Reading Maimonides in this light, systems biology diagrams, as a representation of illness, may promote a false hope about the human capability to treat disease. While research into the best therapy for specific diseases is urgently needed, this aspiration should be tempered by an awareness of the indescribable complexity of the human body, our inability to achieve perfect interventions. The true lesson from systems biology diagrams may be hidden in the web of intersecting nodes and lines—disease prevention is a more achievable “human” goal than curing illness.