3D-printed viruses, synthetic biology and more
The future of war III
Long-time subscribers will know I am a complexity guy, I have an interest in and learning about many fields, besides medicine and molecular biology, and one of my major interests is what used to be my former “job”. Unconventional/Hybrid Warfare, and the future of war itself.
This is a continuation of the piece above, and probably will be an ongoing series on all the rapid progress made in these fields. Before we start with the “theme” of this piece, you must watch this video, from a videogame called Tom Clancy’s The Division (Rest in Peace T_T).
Now I will ask you a question. How “possible” do you think what is portrayed as a fictional plot point in this game is ? How “real” can it be, from impossible, to feasible, to possible, to actionable?
First a few words from the sponsor of this pandemic.
This is a seminal paper written by Ralph Baric, arguably one of the world’s leading synthetic biologists and without a shadow of a doubt the leading expert in Coronavirus research. This paper is from 2007, and technology outpaced even the most avant-garde thinkers and scientists in the last 5 years alone.
Rather prescient isn’t it ? And the costs for what he describes have only gone down. Going back to my question. If you wrote possible or even actionable, you would be correct and possibly picking up certain traits I hope readers pick up.
While we are distant from full organic 3D printing, were you would print a living organism, we are at such advanced stages that the following will read like science fiction.
This entire article is fascinating, but the highlighted sections are really science fiction-esque. DNA synthesis, also called printing is becoming widely available, and while outside the reach of many people if you want to buy the machine (for now in my opinion), you can commercially order them too.
There this company can literally print DNA fragments via synthetic biology, and build new viruses from scratch, costing merely a few hundred dollars per week. For comparison, designing a synthetic poliovirus a little over 10 years ago used cost about 100.000 dollars.
In, and on itself this is amazing, but this isn’t the end of it.
Scientists are using AI to dream up revolutionary new proteins
In June, South Korean regulators authorized the first-ever medicine, a COVID-19 vaccine, to be made from a novel protein designed by humans. The vaccine is based on a spherical protein ‘nanoparticle’ that was created by researchers nearly a decade ago, through a labour-intensive trial-and error-process1.
Now, thanks to gargantuan advances in artificial intelligence (AI), a team led by David Baker, a biochemist at the University of Washington (UW) in Seattle, reports in Science2,3 that it can design such molecules in seconds instead of months.
Such efforts are a part of a scientific sea change, as AI tools such as DeepMind’s protein-structure-prediction software AlphaFold are embraced by life scientists. In July, DeepMind revealed that the latest version of AlphaFold had predicted structures for every protein known to science. And recent months have seen an explosive growth in AI tools — some based on AlphaFold — that can quickly dream up completely new proteins. Previously, this had been a painstaking pursuit with high failure rates.Deep-learning tools such as proteinMPNN have been a game changer in protein design, says Arne Elofsson, a computational biologist at Stockholm University. “You draw your protein, push a button, and you get something that one in ten times works.” Even higher success rates can be achieved by combining multiple neural networks to tackle different parts of the design process, as Baker’s team did in designing the nanoparticles. “Now we have full control over the shape of the protein,” says Ovchinnikov.
Baker’s isn’t the only lab applying AI to protein design. In a review paper posted to the bioRxiv this month, Ferruz and her colleagues counted more than 40 AI protein-design tools that have been developed in recent years, using various approaches5 (see ‘How to design a protein’)
Since 2020 alone, there has been a revolution in Deep-learning tools, and a somewhat democratization of computing power. To use these types of software you often need a research workstation, often named “enterprise level computer/server” (horrible for gaming, or 3D rendering btw), which costs a “small fortune” between 70.000 to 120.000 dollars. There is a very simple, accessible, and somewhat cheap way around it.
Cloud computing.
In many ways the democratization of synthetic biology is inevitable, and given the governmental response to the pandemic, companies now won’t find much red tape after the “astounding and remarkable” success some pharmaceutical companies achieved with mRNA.
Designing new proteins, as with the piece I shared at the start of this has the same dual-use possibilities as designing novel toxins. And you could theoretically custom order designer proteins if they are the right commercially available size. The right protein, the right amplification method, and your imagination are the limit. There are huge groups of biohackers doing amazing things with cheap CRISPR kits in their rooms and garages on Twitter for example.
The last one is less ominous from a superficial look, but interesting nonetheless.
Taking gene therapy to the next level
Current gene therapies fall short on many fronts: the risk of introducing harmful genetic alterations, the lack of tissue-specific delivery systems, along with high manufacturing costs, all mean that very few patients are likely to benefit from these therapies.
AbVitro was acquired by Juno Therapeutics in January 2016 (now part of Bristol Myers Squibb). Not long afterwards, Vigneault and his colleague from the Church lab Prashant Mali, along with John Suliman, co-founded ShapeTX to develop new RNA-targeted therapies for some of the world’s most challenging diseases. “Our goal is to transform patients’ lives by combining large datasets, artificial intelligence and programmable RNA,” Vigneault said.
The COVID-19 pandemic and the successful use of RNA vaccines against SARS-CoV-2 has boosted research into RNA therapeutics. Unlike DNA-based gene therapies, which cause permanent genetic changes in a cell’s nucleus, RNA therapies carry out their activity in the cytoplasm and are more easily manipulated, without the same risk of unintended genetic effects.
When comparing the two approaches, Vigneault uses an analogy: “If you have a computer problem, you don’t go changing the hardware, you install a software update. It’s the same when trying to fix a genetic problem. Rather than fix it at source (DNA editing), you can upload a patch (RNA editing), which is less complex, more efficient and carries less risk.”
“Our goal is to provide just the RNA as the software update, without the need for a large protein system like CRISPR relies on, which could be recognized by the immune system as foreign and trigger immunogenicity,” Vigneault explained.
The overselling of anything is common in any field, and this one wouldn’t be different, but this isn’t what I want you to pay attention to, but rather the syntax. If you missed the people, this is word for word the same rhetoric used by Harari and everyone who bought into his misconceived, poorly thought out ideas of human biology.”
It is also a good point to send people when they label mRNA-based therapies as not also being gene therapy, but they were first thought of as monoclonal antibody therapies, later shifted towards antibodies.
Now you also understand why the Biden administration approved that atrocious biotech horror.
I will leave the closing remarks to one of the few television works I like (and a literal influence on my scientific thought…)
Indeed, the whole world is a lab now, and tests and gain of function research happen population-wide.
Appreciate all supporters and everyone who shares my Substack !
This occurred to me recently after I saw a video of two Chinese student at a California Univ, discussing in broken English how to create self assembling nano-particles. No one is in charge of any of this, and there are millions upon millions of people experimenting.
Science has no more ethics or morals. There is only the tech. The tech is the ethic and the moral. It it can be done it is just. Which is to say - these people are sociopathic and insane.
I wonder which future we are headed to next; the video game HELL future above, the Dune-esque future where there is a jihad against thinking machines, Charlton Heston's Planet of the Apes future. Regardless, I think that nerds with a desire to play God are going to cause so many unintended DNA consequences that within 200 years, all of humanity will be altered beyond our current comprehension.
God have mercy on our souls, we are all screwed.