Bioengineering: the Life Extension Technology We All Want
Bioengineering has powerful approaches that could lead to cheap, safe, and scalable solutions to aging - but is also the most challenging path.
Human biology is like a computer program, and if we could rewrite the software, we could potentially keep people alive and healthy much longer or even indefinitely. We already have the technology to read and write genetic and epigenetic information in cells, and experiments with genetically modified animals hinted that life-extending technologies for humans could be in reach. In the best-case scenario, anyone could walk into a clinic, get a single injection that rewrites their DNA, and simply remain young thereafter. That’s the ultimate promise of bioengineering, and it’s why, in the long run, it might be the most complete answer of all.
The toolkit is already astonishing. We can read the entire genome of a single cell. We can edit DNA with a kind of molecular search-and-replace. We can skip DNA entirely and hand a cell a temporary mRNA program, the trick behind the COVID vaccines. We can even flip the epigenetic switches that decide what job a cell does, for example coaxing a skin cell to become a nerve cell. These tools reach into a cell far more powerfully than any pill - unlike drugs, that generally just modulate the activity of your existing biological machinery, with bioengineering we can add entirely new capabilities. In principle, new genetic programs could let us break down or excrete the junk that clogs aging cells, rebuild worn-out extracellular components of tissue, borrow cancer resistance and other “superpowers” from elephants, whales and other species, and even make ourselves completely immune to viruses. These are not science fiction, but real projects at various stages of development.
So are we on the cusp of solving aging through bioengineering? So far the answer is no, what’s doable in a lab setting is not so easy to translate into therapies for living humans. There are two enormous barriers (we’ll call them “walls”) to surmount for radical life extension to be achieved through bioengineering, design and delivery, which we’ll delve into below. On the other hand, intermediate levels of progress buy us time, and there are strategies that can make the problem somewhat easier. First, we don’t need to chase down solutions to every aspect of diseases of aging, instead we can target the upstream age-related damage that causes those diseases. That’s called the Geroscience Hypothesis, and it means that when it comes to aging, you can feed multiple birds with one scone. We can also make things easier by mostly staying downstream of normal metabolic processes and instead focusing on repairing the damage that they cause. Repairing damage should generally be safer and easier than preventing it, because you are risking disturbance to your body’s natural homeostasis by attempting to reinvent it. These are not hard rules, in some cases modifying metabolic processes might be the easier solution, such as increasing DNA replication fidelity, but in most cases targeting damage appears to be more feasible in the near term.
What already works
While the walls must be scaled to achieve complete solution to aging, there are plenty of partial wins already in progress.
CAR-T: a patient’s own immune cells are re-engineered to hunt cancer. Already approved and saving lives, it is proof that engineered cells can do remarkable work.
CRISPR-based gene editing: results are starting to arrive. For example, Casgevy has shown over 90% success in treating sickle-cell disease.
Non-integrating “Episome” gene therapies: working genes can now be given to patients. For example, Hemgenix infusions have shown long-term remission of hemophilia B.
siRNA: small-interfering RNA molecules can be given to patients to block harmful molecules from being produced. Patisiran suppresses transthyretin, which appears to be a very effective treatment for neuropathy. Inclisarin blocks the production of the protein PCSK9, leading to lower risk of cardiovascular disease through lowering of the blood lipids that cause it.
New gene circuits: gene therapies targeting the liver have shown promising results for reversing atherosclerotic plaques.
Many more interesting and more powerful therapies are at various stages ofclinical and pre-clinical stages of development. This next generation could help people live longer than expected and, hopefully, long enough to live forever.
With all this going for us, why isn’t aging solved? Because bioengineering runs into two enormous walls.
Wall one: the design problem
The truth is that we don’t actually know what changes to make to cure aging. We have some ideas for how to improve things, sure. Fix point mutations, change genes to longevity-associated alleles, upregulate repair, tumor suppression, and other protective genetic pathways. Unfortunately, that’s not even remotely enough to solve aging.
It’s tempting to assume we’ve mostly figured out human biology based on the sheer volume of academic literature. We haven’t. Of our roughly 20,000 protein-coding genes, we have a decent understanding of only about a fifth of them. And most genes don’t even make proteins; they make RNA molecules we understand far less. Zoom out to how genes interact with to each other, and the map is mostly blank. The unknowns in biology dwarf the knowns.
Now remember that aging isn’t one broken gene. Reversing it will likely require not a few tweaks but new genetic programming on a massive scale. This potentially means thousands of new genes and edits, each of which has to do its job and get along with all the others. Even if you have a promising design (in the lab), how do you know if and by how much it will extend lifespan in reality? Right now this is determined empirically, first by testing the design in model systems like animals, and then clinical trials, a process that takes decades. What if you have two promising designs, but it turns out that in practice they interact negatively, nullifying any benefit or even damaging the patient. Now multiply this slow process by the hundreds or thousands of edits you need to make, the countless combinations of possible interactions, and the decades to test each. This is the design problem, and it is the deepest wall in the field.
Wall two: the delivery problem
Even if we knew exactly what to change, with current technology we couldn’t make the changes everywhere they need to happen.
If all your cells were grains of sand, they’d fill an Olympic swimming pool. Now try to put one dot of paint on every single grain. Spray from the top and the bottom gets nothing; flood the pool and the top gets too much. That’s the current state of gene delivery. It’s easy to edit a cell in a dish, yet almost indescribably hard to get the right edits, in the right doses, into all the trillions of cells in a living adult.
Today’s delivery vehicles such as viruses or lipid nanoparticles are limited to payload sizes smaller than many single genes (let alone complex genetic circuits), often provoke the immune system and/or are toxic except in very small doses, and fail to distribute evenly throughout the body. Delivery is not just holding up the big ideas that will solve aging, but even most of the simple ideas we already have. Take the gene variant ApoE4, which causes early onset Alzheimer’s Disease - we’ve known about it for over three decades, but our primitive gene delivery technology cannot fix it. Solve the delivery problem and an armada of new gene therapies could rapidly be brought to the market.
The honest timeline
Bioengineering has no roadmap and barely even a sketch of what one might look like. Rough guesses for a complete solution to aging range from five years (counting on vastly more powerful AI), to over a century because even with AI there is real world friction in data collection and trials that have to run at “normal time”. Some problems like the accumulation of DNA mutations and chemical damage to the extracellular matrix have essentially no plausible proposed solutions on the horizon - it’s easy to be pessimistic.
However, not having a complete solution soon doesn’t mean having nothing. Progress comes in phases: first simple therapies that fix a few specific problems, then optimized genomes that make living to 100 ordinary, then eventually the deep genetic software upgrades that push past the natural limits to human lifespan. People reliably overestimate what can be achieved in a few years but underestimate what will be achieved in a few decades. The last few decades gave us CRISPR gene editing out of nowhere. The next few will hopefully surprise us too.
Where you come in
Bioengineering is ripe with opportunity. It is already the best-funded part of the whole longevity field, with enormous quantities of money and talent from the broader biotech world pouring into gene editing, delivery, and reprogramming. The question isn’t how can we do more, but rather how do we focus time and attention on the right work:
If you’re a scientist, the deepest wall is design: the biology we still can’t read. Work on how genes function and how they talk to each other. Develop better and cheaper data collection, computational models, and faster ways to validate designs.
If you’re an engineer, delivery is the bottleneck gating nearly every therapy: better vehicles to get the right edit into every cell would unlock an armada of them. Don’t work on incremental changes to existing approaches, think out of the box. How could safe and efficient head to toe genetic software updates be delivered?
If you’re a builder or funder, you’ll have your pick of indications and a growing stack of technology platforms: pick a root cause of aging and get a solution to market.
If you’re in government or policy, redirect more funds to fundamental aging biology and hard technology development that private funders are too risk averse or short-termist to touch.
If you’re in AI, help develop models optimized for biology, and (perhaps in collaboration with government) put as much funding as you can towards the deep and extensive biological data that will be needed to train them.
Whatever you choose, the goal is the same: developing technologies that repair age-related damage and thereby extend human lifespan. These technologies will cure age-related disease, but don’t lose the forest for the trees. Curing aging, the underlying cause, is the ultimate goal and ultimate prize. Given our current understanding of biology, this seems certain to happen eventually. What is uncertain is when.
So don’t be content to wait. Dedicate time to moving the field faster. Find an area you like and jump in so we can make these lifesaving technologies available as soon as possible.