Nov 30 2017

Semi-Synthetic Life With Expanded Genetic Code

It’s interesting to follow truly cutting edge research that has the potential to significantly change our world. I include in this category research into brain-machine interfaces, regeneration through stem cells, genetic engineering, and fusion energy. I would also add research into creating synthetic life.

Synthetic life research views living organisms like a technology. It is, in a way, the original nanotechnology, using complex tiny machines to manufacture chemicals, collect and store energy, degrade toxins, and other functions. Scientists have been very successful in tweaking existing organisms to harness them as tiny factories. Many modern drugs are now made in this way, making drugs like insulin widely available.

Some researchers, however, want to go beyond tweaking existing organisms. What if we could create synthetic organisms, even just single cells, entirely from scratch? That is Craig Venter’s dream – to strip down cells to their bare essentials, and then use that as a template to create a completely artificial minimal generic cell. That basic artificial cell, which we understand well because we built it from the ground up, can then be modified to perform endless functions – designer cells.

There is more to this vision, however. Once we free ourselves from the constraints of existing organisms we can explore novel properties that did not happen to evolve. Evolution is powerful, and it has had several billion years to experiment with life, but evolution is also constrained by its own history. For example, all life on earth uses the same genetic code, based upon two pairs of bases in the DNA – cytosine bonds with guanine and thymine bonds with adenine. This produces a 4-letter alphabet for the genetic code (CTAG), and also gives DNA the double-stranded structure and its ability to make copies of itself. The code consists of 64 3-letter words.

Known life is also limited to 21 amino acids with which it constructs all proteins. As an interesting aside, until 1988 we only knew of 20 amino acids. Selenocysteine is the 21st, but it is unusual. It only exists in some branches of life, and it has unique coding. It is coded for by UGA in the messenger RNA (in RNA uracil replaces thymine). But UGA is also a stop codon (a code than ends transcription of the RNA into a protein), so in these organisms this one genetic word can have two meanings. This is just another example of how messy and complex life is.

This genetic code is highly conserved, shared by all known life. What if, however, we could expand the code? That is what researchers are now working on. In a recent paper Zhang et al report that they have created a semi-synthetic organism based on E. coli (a bacterium) that uses 6 bases instead of 4 (or 3 pairs instead of 2) – the pair dNaM–dTPT3 (X-Y) was added. That means there are 216 possible three-letter words rather than 64.

They were able to demonstrate that their semi-synthetic organism was able to decode RNA with the expanded bases and actually function. Further, they were able to incorporate new (what they call non-canonical) amino acids into proteins. They conclude:

The results demonstrate that interactions other than hydrogen bonding can contribute to every step of information storage and retrieval. The resulting semi-synthetic organism both encodes and retrieves increased information and should serve as a platform for the creation of new life forms and functions.

This could mean the ability to create organisms that can direct the production of new proteins that incorporate non-canonical amino acids. This can greatly increase the potential properties of those proteins beyond what ordinary cells can create. Obviously this research is in the early stages, but the results of this study show that it has potential. I also think it reflects how versatile life can be.

When we learn about biology it is often presented as a complex but delicate machine, as if one piece out of place would destroy function. It is certainly true that sometime small changes can be fatal. But in general biology is much more resilient than that. What we see as the complex kluge resulting from evolution is not necessary for any function at all. There is no one correct or optimal arrangement. Many aspects of biology can be changed or removed without destroying function – function, rather, will just be less efficient, or even just have different trade-offs.

We can even mess with the genetic code, and the protein-building machinery will still work. Function won’t be optimal, but it can get by. This demonstrates how new functions can arise through evolution – changes result in new, if less efficient, functions which can later be tweaked and optimized.

It is also interesting to think about the ultimate potential of synthetic biology technology. Without the constraints of history, we can design organisms from the top down. We can eliminate all the junk from DNA, increase its information density, and expand its repertoire. Life is, essentially, nanotechnology. It is fascinating and a little scary to think about the potential of mature synthetic biology.

28 responses so far

28 thoughts on “Semi-Synthetic Life With Expanded Genetic Code”

  1. chikoppi says:

    Synthetic DNA is a fascinating area of research. The minimally viable eukaryotic genome is also an important advancement for establishing experimental controls, as it “resets” evolutionary history to an extent and potentially creates a fully-homogenous population with near-zero variability.

    I don’t know what the replication rate is with these organisms. The LTEE reached 68k generations over 30 years, so I’d assume something on the order of 2k per year under controlled conditions. I hope there are plans to establish a long-term experiment with groups of homogenous semi-synthetic populations divided into both identical and variated environments. I’m curious whether the introduction of new proteins will impact the stability of these populations or the rate of adaptation. Unfortunately, I think it will be quite some time before we learn whether significant any new biological traits can result.

  2. michaelegnor says:

    Great post. I love intelligent design research.

  3. mumadadd says:

    “Great post. I love intelligent design research.”

    You would seriously count humans designing life as reasearch that supports an alternative to evolutionary theory?

  4. mumadadd says:

    By that rationale you should also love climate change research. Humans able to affect the mechanisms of change = proof that design is possible = proof that life/climate was designed by omnipotent super-daddy.

  5. CW says:

    “Great post. I love intelligent design research.”

    Me too when it shows actual testable evidence and methodology like it does in this instance and not assumptions and hand-waving like it does when the DIC talks about it.

  6. hardnose says:

    Don’t worry they won’t evolve to be more intelligent than you.

  7. hardnose says:

    Definitely not more intelligent than me.

  8. chikoppi says:

    [michaelegnor] Great post. I love intelligent design research.

    I realize this is a fly-by trolling, but there’s a point to be made.

    These organisms are specifically NOT designed with a future evolutionary path or outcome in mind. We’ve no idea what additional variations are even possible given the addition of a new base pair or new proteins. If populations of these organisms, isolated in separate environments, were to demonstrate divergent evolutionary adaptation it would serve to further support the core principles of evolutionary theory. There is no design, only variation and constraints.

    [hardnose] Definitely not more intelligent than me.

    Pretty sure they’ve passed that threshold already.

  9. JohnW says:

    Synthetic DNA research isn’t intelligent design research (which is oxymoronic really), it’s intelligent research of design. Intelligent design research is non-existent. No need for research when all difficult questions have the same answer – goddidit.

  10. michaelegnor says:

    Actually there’s an interesting juxtaposition. Lenskis research is (quasi) Darwinian, and this synthetic life stuff is ID research. The differences are notable and obviously support the inference that aspects of biological function are designed. Lenskis work, more than anything, shows the futility of undesigned evolution.

  11. mumadadd says:

    Michael,

    So if I can design a stone, stones in general are therefore designed?

    I can’t see how you don’t know that what you’re saying is obviously ridiculous.

  12. chikoppi says:

    [michaelegnor] Actually there’s an interesting juxtaposition. Lenskis research is (quasi) Darwinian, and this synthetic life stuff is ID research. The differences are notable and obviously support the inference that aspects of biological function are designed. Lenskis work, more than anything, shows the futility of undesigned evolution.

    Nope. Neither.

    What BOTH experiments demonstrate (or would, if there were a synthetic version of the LTEE) is that the outcome of evolutionary processes result in a range of non-directed possibilities. No plan or pre-determined destination is present.

    Genomes of populations with DNA based on two base pairs expand randomly, in both variability and complexity, within the constraints of viability (what produces a functionally replicating organism) and the demands of the current environment. With each generation the frame of variability shifts and the process repeats.

    In the LTEE experiment we see one population that produced a highly adaptive trait and three or four that have developed increased rates of mutation. That is “undesigned evolution” at work.

    We have no idea how three base pairs will change the dynamics of gene mutations or how new proteins might contribute to the evolution of biological traits. If populations with synthetic DNA undergo adaptive evoltion those adaptations are clearly not the result of design, but examples of the same evolutionary processes demonstrated by the LTEE.

  13. michaelegnor says:

    Chi:

    [Genomes of populations with DNA based on two base pairs expand randomly, in both variability and complexity, within the constraints of viability (what produces a functionally replicating organism) and the demands of the current environment. With each generation the frame of variability shifts and the process repeats.]

    Translation: ‘things change and survivors survive’. Quite a “mechanism” ya’ got there.

    Mum:

    [So if I can design a stone, stones in general are therefore designed?]

    Of course stones are designed. Each particle/atom in a stone is described by Schrodinger’s equation. How is it that inanimate matter is so well described by such elegant mathematics?

    Just happened, for no reason, I guess.

    Atheists are such asshats.

  14. chikoppi says:

    [michaelegnor] Translation: ‘things change and survivors survive’. Quite a “mechanism” ya’ got there.

    You sound as foolish describing evolution in those terms this time as you did the last.

    So long as those who pout and grouse about evolution are reduced to attacking strawmen they’ll continue to be rightfully and summarily dismissed.

    Of course stones are designed. Each particle/atom in a stone is described by Schrodinger’s equation. How is it that inanimate matter is so well described by such elegant mathematics?

    The math was invented to describe the observable universe. The universe did not fall out of the math.

    What would a universe look like that wasn’t quantifiable or describable?

    Atheists are such asshats.

    You have amply demonstrated your own enthusiastic embrace of behaviors associated with that monicker on occasions too many to recount. It’s like a clown trying to tell someone else they look silly.

  15. bachfiend says:

    Michael,

    ‘Of course stones are designed. Each particle/atom in a stone is described by Schrodinger’s equation. How is it that inanimate matter is so well described by such elegant mathematics?’

    No they aren’t. The wave function of single isolated particles (eg electrons, atoms) are described by Schrodinger’s equation. The same applies to collections of atoms such as in a stone – there’s a single wave function for the entire stone, not numerous wave functions, one for each of its component atoms, as you seem to think.

    And the length of the wave is very small, so that the location of a stone can be measured with extreme precision, unlike an individual electron which has a non-zero probabity of being anywhere in the universe.

    How you get from Schrodinger’s equation to the assertion that stones are designed is a mystery. It’s also is a non sequitur. We live in a universe that has physical regularities that allows the formation of stones. And stars and planets. If stones couldn’t form, then neither could the Earth. Nor us.

  16. bachfiend says:

    Michael,

    ‘Things change and survivors survive.’

    You’ve got a very inaccurate simplistic formulation of evolution there.

    If you want a simplistic formulation then it’s more accurate to state that ‘populations change as individuals within the population survive longer to have more than the average number of offspring.’

  17. Willy says:

    Asshats–What a razor sharp intellect.

  18. JimV says:

    I think the key point IDers are missing is that human research, design, and intelligence is basically an evolutionary process. Ideas can occur randomly, such as Edison trying hundreds of materials for the filaments of incandescent light bulbs, until he found bamboo fiber, or by modifications of things observed previously, such as logs rolling downhill -> rollers under heavy weights -> wheels on axles -> gears, etc.

    It is not a magic process, but a trial-and-error process. Haley’s watch and the trees around it were similar in that both evolved. Good ideas survive and reproduce through generations until better ideas replace them.

    Human design work, such as the trial-and-error effort which led to a synthetic form of life, is not evidence for a magical creator. It is more evidence for the power of the evolutionary algorithm.

  19. bachfiend says:

    JimV,

    Good point. Though you meant ‘Paley’s watch’.

    I once had an argument with a creationist who insisted that a cell was much more complicated than New York. New York was designed, so therefore the cell was also designed.

    Except New York also evolved. No one back in the 17th century had a plan for the city. Things just got added, removed and modified over the centuries. Buildings got built, then torn down, or burnt down, and replaced with other buildings. Earth tracks got cobblestones then paved. Tramlines were built then removed. Railway lines were constructed. Subways. Numerous unpredictable changes were made to meet current and currently expected needs.

    Town planning is almost an oxymoron.

  20. BillyJoe7 says:

    The other point is that it is so blindingly obvious that “The Universe is Intelligent” and “God is The Ground of All Being” are not explanations for anything. You still have all your work cut out for you. You have to explain where this “intelligence” or “god” came from.

  21. Drake says:

    I once had an argument with a creationist who insisted that a cell was much more complicated than New York. New York was designed, so therefore the cell was also designed.

    An odd thing for the creationist to have said. A fundamental component of New York City is its 8.5 million human inhabitants. Each of which consists of some 30 trillion cells. It’s hard to see how ‘complexity’ could be defined, such that a single cell would be *more* complicated than ~10^20 cells, all interacting in some way with each other.

    I’m trained as a designer, and have long been of the opinion ID’s misunderstanding of (human) design is at least as profound as its misunderstanding of evolutionary biology.

  22. bachfiend says:

    Drake,

    She (the creationist) was referring to the infrastructure of New York, not the people. The roads, buildings, water, gas, electricity supplies, parks, etc. including the people in her conception of the complexity of New York would also mean it would be necessary to include all the water molecules, electrolytes, etc in the ‘complexity’ of the cell, in which case the cell would still ‘win’.

  23. hardnose says:

    “Except New York also evolved.”

    Yes it did. And so did all human technology and culture. It evolves, AND it is designed. The two things, evolution and design, don’t exclude each other.

    You should know, but you don’t, that Intelligent Design theorists DO BELIEVE in evolution.

  24. hardnose says:

    “It is not a magic process, but a trial-and-error process.”

    Creative/inventive projects usually involve trial-and-error. But they are not simply trial-and-error. Nothing useful, or beautiful, was ever created simply by random trial-and-error.

    This should be obvious.

    The human inventor’s mind is involved in the process. You know this, because it is obvious, but somehow materialist doctrine makes you forget?

  25. chikoppi says:

    [hardnose] Creative/inventive projects usually involve trial-and-error. But they are not simply trial-and-error. Nothing useful, or beautiful, was ever created simply by random trial-and-error.

    Define “useful” or “beautiful.”

    How about viruses or prions that cause brain damage? They are certainly functionally effective, complex, adaptive, and often quite lethal. How about the near infinite varieties of a snowflake?

    None of these things are designed. These forms follow relatively simple physical constraints which then govern interactions with the environment around them.

    This should be obvious.

    The only people who say things like that are those who are to lazy and intellectually dishonest to actually study a subject. All the countless wrong notions that have ever been overturned by science were those that were “obvious” to the naive and uneducated.

    The human inventor’s mind is involved in the process. You know this, because it is obvious, but somehow materialist doctrine makes you forget?

    As someone who has actually studied design (that’s my undergrad degree) and philosophy and has bothered to learn something about evolutionary science, I can safely say that I’ve forgotten more on these topics than you’ve ever known. You could remedy that, if you’d only bother to learn rather than repeatedly and shamefully proclaiming your self-imposed and quasi-religious fidelity to metaphysical ideologies. Grow up.

  26. bachfiend says:

    Hardnose,

    ‘You should know, but you don’t, that Intelligent Design theorists DO BELIEVE in evolution.’

    So you’ve finally gone from a nebulous Intelligent or Conscious Universe to an Intelligent Designer?

    Kenneth Miller’s argument against the so-called Intelligent Designer is that it’s not particularly intelligent or competent. The history of Life on Earth is that at least 99.9% of species have gone extinct. The Intelligent Designer allows most of the species go extinct and then designs new species, often very similar to the extinct ones, to replace them.

    It’s difficult to pin down what ‘Intelligent Design theorists’ actually accept. Stephen Meyer in ‘Darwin’s Doubt’ finally admitted his Intelligent Designer is God. Other ID proponents are out-and-out Young Earth Creationists.

    Their acceptance of evolution is a matter of what evidence they can’t deny without appearing silly, something you’re perfectly willing to do whenever you comment. Deny the evidence and appear silly.

  27. Drake says:

    Creative/inventive projects usually involve trial-and-error. But they are not simply trial-and-error. Nothing useful, or beautiful, was ever created simply by random trial-and-error.

    This should be obvious.

    The human inventor’s mind is involved in the process. You know this, because it is obvious, but somehow materialist doctrine makes you forget?

    Hardnose, the way you use the word ‘obvious’ suggests someone sucking down the greatest meal imaginable as if it were nothing but calories.

    ‘Creative,’ ‘inventive,’ ‘useful,’ ‘beautiful,’: what those concepts might mean, and how they could apply to the world, ought to be a banquet to occupy anyone a good long time, not just terms to be swallowed whole and shit back out to argue a point.

    Years ago, when I was a cook, I worked with a waiter who had no sense of smell, and consequently, little ability to taste. I hate to pity anyone, yet I pitied that guy.

    For analogous reasons, I find myself pitying you, stuck as you are in such a bland worldview.

  28. JimV says:

    Thanks for the correction on Paley.

    Yes, evolution is more than trial and error. My general definition of the algorithm briefly is:

    1) Some way to generate trials (including randomly).

    2) Some selection criteria to separate successes from failures on some sort of scale from good to neutral to bad.

    3) Some form or forms of memory, to pass successes on to the future.

    1) and 2) can be summarized as trial-and-error, but there is no need for trial and error when a good solution exists in memory. E.g., good engineers check Mach’s handbook and other sources. They don’t start from scratch on every problem – but neither does biological evolution. Bacteria have a huge library of previously-developed genes (in some cases more than the human genome). When evolving a new function, as Lenski’s E. coli did, they are able to use those genes as a starting point.

    Niels Bohr said, “An expert is someone who has already made every possible mistake in a narrow field.” Which is to say, trial and error does play a huge part. In 38 years as an engineer designing parts for steam and gas turbines, I have never been part of a project in which it did not. (Mainly because steam turbines are custom-designed for site and boiler conditions, so there are no standard designs unlike, say, toasters.) In any case, I have never seen any magic involved in human design work. After all, humans have been around for about 154,000 years (latest archaeological data, last time I checked), and the earliest archaeological of the wheel is about 6000 years ago – it took us roughly 148,000 years to design the wheel. Past the initial hurdles, though, evolutionary progress becomes exponential (until it consumes the available resources) – thanks to memory.

Leave a Reply