• Melanie Matheu

Generative Design v. Evolution for Replacement Human Organs

Should we, if we could build a ‘better’ alternative to the human organs?

Whether or not you think it’s a good idea to design a human organ to match known biology comes down to one simple question: can we build something better than evolution’s version of organ engineering?

Since founding Prellis Biologics, Inc. the human engineering company with a mission to print any organ structure, true-to-form, I’ve had a phenomenal series of conversations on this topic. Everyone from Venture Capitalists, to thought leaders, Physicians and Biotechnologists love to discuss what it takes to build a real human organ replacement: And perhaps even more interesting, could we build something better?

In the last couple of years organ engineering technology has moved from science fiction firmly into the realm of possible. With this comes a deeply important question: should we use Generative Design or rely on Evolution’s version of organs to recreate tissues for transplantation?

Human organs function well. In fact, without any significant exogenous health issues, Kidneys, Hearts, Livers, and Lungs are capable of functioning through an 80 to 100-year lifespan, as designed.

Few, if any, engineered products that have similar stresses and strains applied daily can say the same.

So why, when given free reign to print any biological structure imaginable do we feel the need to tinker or overhaul what so clearly works?

The imagination is an exciting place. We’ve seen bionic robots, Westworld, and have dreams of building something better, faster, stronger than what we were born with.

Or, perhaps as some have brought up in our discussions, evolution took a wrong turn somewhere? Are our Kidneys a tissue that long ago settled into a functional local minima of physiologic sufficiency?

Several conversations I’ve had land on the idea that it’s possible in our collective history that one organ design worked sufficiently well (but not best) and our ancestors headed down a

path of evolutionary least resistance.

Maybe, instead, humans could have developed a heart that would beat for 600 years once a minute, or a brain that didn’t need us to truly ever fully shut down for sleep (much like that of a dolphin).

A common ethical point of debate that often arises in these conversations is much like the recent ethical issues with CRISPR and rapid human evolution.

Should we, even if we could, give people Kidneys that are orders of magnitude better, or lungs that allow athletes to will break all world records? Are we on the horizon of human speciation for those who can afford it?

If you could print anything what would you start with?

Our company’s first mission in organ engineering to rebuild what we know already works, or to get as close as we can, and we have reasons for this. Not because we’re unimaginative scientists afraid to think out of the box, but because decades of specific training in the field and musings on exactly these questions.

Personally, my PhD training as a Physiologist & Biophysicist with a heavy emphasis on Immunology left a deep impression on me regarding the complexity of organ systems. But my multi-decade appreciation started in my first Medical Physiology course I took at 18. We studied the intricacies of each organ system over the course of 3 months alongside first year medical students.

From there, decades of study I’ve come to the conclusion that it’s not necessarily that organs are complex, but that the physical design and it’s tremendous intricacies are what allows an organ to function. I’m referring specifically to surface to volume ratios and packing densities that allow for gas and nutrient exchange to be more efficient than any bioreactor or filtration system the human race has ever built.

To redesign those systems into similar sized structures while meeting the basic requirements of human physiology is an engineering endeavor no one has ever achieved. Not even on paper. Not even in silico with AI.

I still believe it may be solved in the future, but as it stands now, we have no generative designs that could match the efficiency of a human organ.

Unlike other bioprinting companies and technologies — Prellis Bio isn’t relegated to developing a generative design, because we can print a true-to-form tissue. Therefore, our logic going forward was to build what we know should work. As my graduate school professor would often say: “Solve one hard problem at a time.” and I believe he is still right.

To consider generative design as the first option would not only ignore that several engineers before us have determined this to be a thus far an intractable problem, but to ignore another fact of cell biology.

Human cells and physiologic systems are set up to depend upon intrinsic and extrinsic signaling. Organ development and cell behavior rely on environmentally triggered feedback loops.

Cells behave and respond to specific tissue geometries and changing those factors alone can significantly alter gene expression and shift tissue development down a non-productive path. Organs and vasculature will remodel, become fibrotic, or simply stop working if extrinsic signaling pathways are significantly disrupted.

Furthermore, our organs are part of a system that relies on the capacity of other organs and there is important cross-talk between these systems. If you suddenly have a heart or kidneys that are 80% more efficient how will that alter physiologic function of the rest of the organs? Would a patient even survive this augmentation?

In short, no one is saying evolution didn’t take a wrong turn. Perhaps our systems design is simply stuck in a local entropic minimum of design + efficiency. But I have yet to encounter a physiologist in favor of generative design as more than a teaching problem.

Personally, I’m completely open to the idea of exploring better options with our technology, but not at the expense of doing what we already know works.

Today, there are millions of people who will die without a life-saving organ transplant. If we already have the roadmap to success for these patients in hand, why not follow it?

When we achieve the medical breakthroughs that will allow full human organ replacement from lab-grown tissues, there will be time, perhaps more time for all of us, to explore improvements in human organ systems through engineering.

#Science #Startup #Engineering #TissueEngineering #GenerativeDesign