Design Thinking: A Method for Building Creative Immunity

Principles of design thinking share an interesting origin with mechanisms of adaptive immunity

One of the most counter-intuitive principles when applying design thinking to healthcare and surgery specifically is the idea that quantity of ideas is initially more important than quality of ideas. Then there is the even stranger notion that ideas that seem "out there", "impractical", or even "bad" are still worthy of consideration, experimentation, and evaluation.1 As healthcare providers, our traditional research methodologies often focus on refining ideas against known constraints prior to experimentation rather than throwing everything against the wall to see what sticks. "That will never work" is a common refrain in brainstorming sessions. However, to understand the true potential of divergent ideation and creative brainstorming, we need only look inwards at one of the most essential players in our field: the antibody.

Antibodies are without a doubt one of the miracles of human life (and that of other species - as they evolved in jawed vertebrates 500 million years ago). The principal function of the antibody is to recognize non-self particles and direct the immune response to neutralize them. At the risk of over-simplification, foreign agents such as bacteria and viruses contain unique surface molecules. Oftentimes, these surface molecules are used to gain entry into host cells and cause infection. However, these molecules also serve as unique signatures (keys) that distinguish the invading agents as foreign. Antibodies bear unique counter-signatures (locks) that can recognize and bind foreign keys. Once bound (key-lock combination), the antibody neutralizes the offending agent and directs the immune response towards agents bearing a similar key signature. How then, can an antibody generate a lock for an infinite number of keys - none of which it has yet encountered?

Antibodies are made by B cells, named eponymously for their origin in the bone marrow. Each B cell contains in its DNA the code for one unique antibody. Antibodies are Y shaped molecules.2 While the legs of each Y are shared among all antibodies, the tips of each prong are variable and contain docking sites (locks) for potential foreign keys. The shape of its docking site is what makes each antibody unique. The structure of each docking site is made up of three types of building blocks. Rearrangement and reassortment of the DNA encoding these building blocks creates unique combinations that translate into different shapes - a process called recombination.3 But that is only part of the magic. Small errors made in the DNA fragments that bind each permutation of blocks together generates a limitless repertoire of possible locks. The process is tightly regulated – left uncontrolled, it can lead to cancer or autoimmune dysfunction. But when orchestrated with precision, it allows for the immune system to adapt to nearly any pathogenic foe.

Once a corpus of diverse antibodies is created, the body needs to figure out which potential locks are useful and which are useless or even potentially harmful. During infection, immature B cells display their unique antibody on the cell surface and are exposed to foreign molecular keys. Cells bearing antibody locks that match the keys are allowed to replicate, those that do not die off. Conversely, cells producing locks to self keys are also prevented from replicating. This process is known as clonal selection.4 Even after the antibody is activated by a match with the key of a foreign pathogen, it continues to undergo refinement. As selected cells replicate, random changes are introduced in the variable prongs of the antibody. Over several rounds, this somatic hypermutation yields some docking sites that better fit the foreign key. The stronger the affinity between the lock and key, the more the cell bearing that antibody is allowed to replicate – a phenomenon known as affinity maturation. Over time, the strength of the initial lock-key combination is increased thousand-fold. (For a much more detailed view into the relationship between the immune system and creativity, read this paper).5

We can learn a lot from the example of the antibody. Recombination demonstrates that instead of trying to find a winning idea, it is better to come up with as many ideas as possible. Rearranging existing ideas is a useful place to start, but some reliance on randomness is just as important. The principles of clonal selection and affinity maturation teach us that prototypes should be tested and refined iteratively. Experimentation, not intuition, should pick winners and losers. From somatic hypermutation, we learn that even initially successful ideas should not be immune to further brainstorming and refinement. As educational psychologist Gary Cziko wrote, "the immune system does not attempt to predict the antibody structure that will bind with an antigen, but rather uses a type of shotgun approach that sends in a diverse army to meet the invaders". Aspiring design thinkers too must send a diverse army of ideas to meet the pressing problems of our time.

Design thinking is a relatively new, experimental field. Though it has an established track record of spurring innovation in industry, its introduction to healthcare and surgery remains nascent. To those who remain skeptical of its promise, it may be helpful to think of it as a model based on a biological principle nearly 500 million years old, described by multiple Nobel prize winning scientists, and essential to our very survival. To extend the metaphor, the antibody's most impressive feat is to generate immunologic solutions to a pathogenic problem it has not yet encountered. While rigorous testing against the pathogen itself will lead to refinement, propagation, and dissemination of winning solutions, it must first exist as a rudimentary prototype within the immunologic substrate. Applying this logic to our ideation process against challenges in healthcare, perhaps divergent and broad ideation can help generate a form of creative immunity - the ability to design for the challenges of both today and tomorrow.

1. These and other principles of design thinking are captured in the book Ideaflow by Jeremy Utley and Perry Klebahn.

2. The structure of antibodies was discovered by Gerald Edelman and Rodney Porter, who shared a Nobel Prize in 1972 for this discovery Link to papers here and here.

3. This process is formally known as VDJ recombination. It was discovered by Susumu Tonegawa, who won the Nobel Prize in Physiology or Medicine in 1987. The proteins responsible for orchestrating this recombination were discovered by David G. Schatz and Marjorie Oettinger, and David Baltimore. Interestingly, Baltimore had already been awarded the Nobel Prize for previous contributions to virology.

4. The theory of clonal selection was developed by immunologists Niels Jerne and Frank Macfarlane Burnet who won the Nobel Prize in Physiology or Medicine in 1960 and 1984, respectively.

5. In doing research for this essay, I came across the paper How the Immune System Deploys Creativity: Why We Can Learn From Astronauts and Cosmonauts written by Henderika De Vries et. al. The paper provides a much more detailed and scientific description of the relationship between the immune system and creativity.

6. RE: all of the above, should I be studying immunology!?


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