Hey, a project I actually know about. Used to work in Kaisha Benjamin's lab (Endy Lab at Stanford). I remember all those bioinformatics to get the glucose inducible promoter. Back then at least, the promoter wasn't controllable enough. Currently, I'm actually vaguely helping with this project by synthesizing phage PH15 (building a high throughput DNA synthesis/assembly company right now). Can probably use the phage to package up DNA to transform S. epidermidis.
In general, I think microbiome engineering is super cool and should be explored more!
Really cool area for emerging biotech. Insulin production circuits like the ones described in this article have inspired (and frustrated) synthetic biologists for a long time.
For anyone who approaches biotech with an engineering mindset, insulin makes for a very clean and well-posed problem.
1) Medical insulin is already produced by engineered microbes, and has been for 40 years. So we know microbes can do this safely and effectively.
2) Insulin is a single gene, so it's easy to engineer. We can move it around to different organisms and add different control systems to explore where and how it is expressed.
3) Diabetes is a well studied disease. We know a lot about how much insulin patients need, at what times, in response to what signals. So it is a well defined engineering problem.
4) There is a clear medical need for better diabetes treatments and a large profitable market for anyone who can deliver them.
Personally, I'm not sure that engineered microbes are going to be the best answer for delivering insulin to patients in real time. There are just so many alternative ways to deliver insulin. You'd have to really deep dive on a lot of options to decide which tech was most promising.
But insulin as a challenge problem has driven a lot of innovation in engineered live microbial medicines, including for applications where a microbe is really the only logical answer.
Check out the latest data from synlogic, for example, on live microbial therapies for other metabolic diseases: synlogictx.com/clinical-trials
Its a neat headline, but its unclear what problem this is trying to solve. I hope the first viable versions it don't colonize the poor grad student.
I think these analogies miss the forest for the trees. This is a wholly different idea and approach than prior art related to insulin, synlogic's trials, or fermentation (the production of products by microbes in a reactor)
> 1) Medical insulin is already produced by engineered microbes, and has been for 40 years. So we know microbes can do this safely and effectively.
This is in a sterilized tank with defined media and careful controls, not on a human body.
> 2) Insulin is a single gene, so it's easy to engineer. We can move it around to different organisms and add different control systems to explore where and how it is expressed.
Syn bio control systems are so coarse and unreliable I would never trust my life to one. Would you?
> 3) Diabetes is a well studied disease. We know a lot about how much insulin patients need, at what times, in response to what signals. So it is a well defined engineering problem.
We do, but microbes don't
The synlogic trials are essentially for augmented digestion, something we've always relied on microbes for. That's a lot safer than a feedback-control mechanism for an essential hormone.
This is the creation of a (hopeful) symbiosis with the hope that the steady state for one organism is also the optimal steady state for the other.
This idea is also the release into the wild of an organism designed to live on or in humans with the hope it does not become a pathogen, and the hope that its host will never enter a metabolic state where it assumes the role of a pathogen.
Isn't this just gain-of-function research with another name? Feedback and control in syn-bio is coarse to say the least. Is it responsible to be developing this tech with a microbe that can live on mammals?
I must add, I am _profoundly_ pro-syn-bio. I think this field needs to take itself more seriously before something bad happens.
> There is a clear medical need for better diabetes treatments and a large profitable market for anyone who can deliver them.
True, but with the exception of type I diabetics (a relatively small proportion of all diabetics, about 3% of total), the goal is to avoid insulin treatment.
What you want to do is reverse insulin resistance, while restoring blood glucose control. Basically reverse metabolic syndrome. That's what the therapies like SGLT2 inhibitors, GLP1s, DPP-4 inhibitors, etc.
If a type II patient gets to the point of needing exogenous insulin, you've basically reached the end of the line.
So what happens if the bacteria spreads to people's guts when they don't have diabetes? Seems like a risky thing, or maybe it would be rare like autobrewery syndrome.
The original holder of the insulin patent gave it away free - and yet thousands of American families have struggled to pay for it:
https://www.rand.org/pubs/articles/2021/the-astronomical-pri...
I get that this engineering is cool. I think there are other ways to ensure that American families have access to medication.
The best way to develop GMO technologies is to regulate it after it injures millions of people. And that regulation is... declaring anyone who questions the science a terrorist.
While full of interesting facts, this idea is so scarily bad it’s hard to justify.
If ginkgo has a theranos style meltdown this will be an article we can look back on and think “I guess they were telling us all along and we should have seen it”
Not one of their projects, but published by their magazine.
If AWS had an industry magazine that proposed data centers could be run by well-trained dogs, I'd definitely sell my shares.
Synthetic biology safety needs to be taken more seriously than anything our society has ever invented. Removing synthetic organisms from of a lab can have such dire, irreversible consequences we can't even begin to predict them. Jurassic Park mixed Ice-9 from Vonnegut's 'Cats Cradle' is a near approximation of the possibility.
Eh. Most people I see who are super concerned about synthetic biology safety aren't the people actually working on it (in contrast to things like AI, or even more innocuous technology like social media). That includes me. I've worked in synbio for >10yr and consistently the danger is overhyped by people who don't get it.
> dire, irreversible consequences we can't even begin to predict them
No, they're dire consequences that you can't predict, probably because you don't work in the field. There are lots of ways to predict what could happen.
Fair on the gatekeeping, but on the other side, keep your mind too open and your brain will fall out.
> This is precisely the problem I’m pointing out.
This is, ironically, also the problem I’m pointing out. Why would I trust someone who doesn’t work in or on computers in computer security?
Arguing that once the promise is shown it’ll become super dangerous is essentially unfalsifiable. The same argument can be made for literally any new technology. I’d like to see reasonable chains of logic.
> Why would I trust someone who doesn’t work in or on computers in computer security?
I think you misunderstood my comment. I'm deeply familiar with this field. I know very much what I'm talking about.
> The same argument can be made for literally any new technology
Asimov pointed this out a long time ago. This is the first time our technology has had the ability to replicate and modify itself for its own benefit before we started engineering it. As somebody who's engineered viruses, I know how easily something like COVID could have been a lab leak without any malicious intent.
Let's say we engineer a better nitrogen fixation pathway and give it to a microbe to help crops. What happens when that microbe washes into a nearby stream, river, watershed and then discovers its better off without our crop. What's to stop it from giving the nitrogen to the water around it, causing algal blooms, oxygen starvation, and dieoff? Preventing its spread would be impossible and could lead to the destruction of freshwater ecosystems. This is just a mildly-plausibly hypothetical, but I also know there are active experiments like this in the United States right now, in outdoor test plots, and the safety in place is just people like you and me who are 'policing ourselves'
In general, I think microbiome engineering is super cool and should be explored more!