Virus-proof cells?

I am very skeptical about the pronouncement this week that a group of scientists plan to engineer cells to resist virus infection.

The initiative is called Genome-Project-write (GP-write) and is composed of an international group of collaborators with the broader goal of designing and assembling a synthetic human genome. The first goal of this consortium, reported in Science (“Genome writing project aims to rally scientists around virus-proofing cells”), Time (“Scientists announce plan to create virus-proof cells”) and many other news sources, is to create human cells that cannot be infected with all known viruses.

Could such virus-proof cells be made, and what would they be used for?

Jef Boeke, one of the directors of GP-write, said “There is very strong reason to believe that we can produce cells that would be completely resistant to all known viruses”. But science is not a belief system – it depends on facts, and I know of none that would predict that cells can be made resistant to all the viruses we know about. Boeke’s statement sounds like it was designed not to reflect facts, but to raise money.

GP-write’s plan is to change the codon usage of human cells so that they will not be able to support translation of viral mRNAs. Multiple mRNA codons may specify the same amino acid, and the plan is to eliminate this redundancy. But multiple codons exist for a reason – among others they provide a buffer against lethal mutation. Recoding the human genome in this way is not likely to be without serious side effects.

More importantly, how do we know that recoding the genome would inhibit virus infection? The organizers of GP-write cite as their proof of concept a 2013 paper in which all known UAG stop codons of E. coli were replaced with a UAA stop codon. The cells displayed increased, but not complete resistance to bacteriophage T7. Yet in an enormous stretch of the facts, Torsten Waldminghaus says “It worked in E. coli, and I would expect it to work in human cells also”. Perhaps Waldminghaus and Boeke have similar belief systems.

The fact that the recoding strategy barely worked in E. coli for one bacteriophage in no way implies that it would work in human cells. We do know that some viral proteins have altered codon usage, but to suggest that one recoded human genome would suffice to inhibit translation of all known viruses is simply dreaming.

I’d also be willing to bet that viral genome mutations could be selected that would overcome the limitations of a recoded human genome.

But let’s assume that human cells could be made that are resistant to all human viruses – what would they be used for? George Church, another GP-write director, has said “Ultra-safe cells could have a major impact on human health”. Is he thinking of introducing virus-resistant cells into humans? If so I would offer a few reasons why it would be a bad idea to make humans resistant to all known viruses:

  • Infectious viral vaccines would no longer work (but I suppose you would not need them)
  • Viral gene therapy would no longer work
  • Oncolytic virotherapy would no longer work
  • Our beneficial viruses would no longer work
  • Unknown viruses would still be able to infect us

The goal of making virus-resistant cells is simply a talking point for attracting funding so the organizers can achieve their goal of synthesizing a complete human genome. But in my opinion having a goal of making virus-resistant cells takes away the credibility of GP-write. The plan is so shaky, so not based on what we know, that it makes the organizers seem as if they have not completely thought about the details. I would be astonished if their potential funders buy into this idea. GP-write’s contrived project can only serve to further undermine trust in science.

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