What’s new with GMO?

Today I’m going to do things a bit differently.

I‘d like to encourage my followers to read several articles I just found out about. So here are several interesting pieces of news regarding CRISPR, a new gene-editing technique and a couple of links to the first ever completely synthetic, artificial cell:

Please read all of the above articles and educate yourselves. This isn’t in the mainstream news, but it should be.

I should probably state here that I don’t even pretend to know about genetics. I’m not a geneticist, I studied Materials Science.

All I do know is that nature has laws and you cannot break those laws. Bacterial diseases are lifeorms too and they are just as robust and ‘innovative’ as even the cleverest of humans.

I think that scientists often tend to overestimate their own intelligence level, and at the same time, underestimate the resourcefulness of nature itself. I don’t think we can ever fully predict the “revenge effect”. But it is there. The risk is always there.

I’m sure the field of genetics is really, really advanced by now. I’m not saying that it’s not. But the big worry for me is just that— as science becomes more and more and more specialised, people get ‘cleverer’ but they don’t always become ‘wiser’. So to put that another way, the greatest geneticist minds may claim to know all about genes, and they might even be right, but then they cannot also be the greatest experts in ecosystems. The fields of science are that big today that no one can know everything. It’s impossible! That’s the big worry.

“I don’t think it represents the creation of an artificial life form,” said biomedical engineer James Collins at Boston University. “I view this as an organism with a synthetic genome, not as a synthetic organism. It is tough to draw where the line is.” [source]

So it’s frustrating for someone like me with a more ‘general’ overview of “how the world works”. Because straight away I’ll be shot down in flames for not knowing enough about gene sequencing or whatever by people that know much more than me.

But my main question to geneticists is this: if we haven’t even discovered much less documeted all of the species of life on Earth yet, let alone genetically sequenced them, how can we ever know what the full effect of editing genes in once species is going to have on the interactive dynamics of an entirely complex ecosystem?

I’ll say that again because it bears repeating, if we haven’t sequenced all of life yet, how the fuck can scientists even begin to predict how entire ecosystems are going to respond in the wild? You don’t even know fully what variables you are playing with yet, let alone all of the possible interactions!

“We make a genome from four bottles of chemicals; we put that synthetic genome into a cell; that synthetic genome takes over the cell,” said Dr. Gibson. “The cell is entirely controlled by that new genome.” [source]

The fact is, evolution is blind. And so is this. Life is complicated. Yes you know a lot. Brilliant! But even so, this one suspects that you still only partly know what you are doing.

According to Dr. Hutchison, “To me the most remarkable thing about our synthetic cell is that its genome was designed in the computer and brought to life through chemical synthesis, without using any pieces of natural DNA. This involved developing many new and useful methods along the way. We have assembled an amazing group of scientists that have made this possible.” [source]

When geneticists can tell me EXACTLY how and why a leopards’ spots appear where they do, then we may be ready. Or when geneticists are able to grow a tree with multi-coloured bark that reads like a speed limit sign, you know, with the numbers 60, with a little circle around it and everything in reflective red and white, then we may be nearly ready for this technology. Then, once you have figured that much out, dear geneticist, go and read about complexity theory, about chaos theory, to round out your knowledge. Then come back to me and I’ll start believing you when you say you know what you think you are doing.

“What we’ve done is important because it is a step toward completely understanding how a living cell works,” says Clyde Hutchison, who co-led the study. “If we can really understand how the cell works, then we will be able to design cells efficiently for the production of pharmaceutical and other useful products.”

Their first stab at a minimalist cell failed. “Every one of our designs failed because we based these on our existing knowledge base,” says Venter.

It later turned out that some genes they had thought were not essential were crucial – but because these came in pairs, the organism could still survive if only one of them was removed. When they realised this, they could more reliably whittle down the genome and still maintain a living, growing cell.

“To get a viable cell, the researchers needed to make discoveries about many essential and semi-essential genes that we did not know about,” says Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida.

The big surprise was the discovery that some 31 per cent of the essential genes have no known function.“We discovered some essential facts of biology by doing this,” says Venter. “It means we know about two-thirds of essential biology, because we are missing a third, which is a very important lesson.”

Hutchison says it is an “exciting possibility” that some of the genes perform essential biological functions that are currently unknown.

It’s unclear how genes of such universal importance have ducked under biology’s radar for so long. It could simply be that they code for known functions, but are just not similar enough to equivalent genes from other organisms to be recognised as such yet.

“Finding so many genes without a known function is unsettling, but it’s exciting because it’s left us with much still to learn,” says Alistair Elfick, a bioengineer at the University of Edinburgh, UK. “It’s like the ‘dark matter’ of biology.”

No, I don’t think we’re anywhere near ready for this yet.

If there is one thing that materials science has taught me, it is that little fluctuations or changes in a materials’ atomic structure, molecular structure and microstructre can (and usually do) lead to big changes in their macroscopic (bulk/visible) properties. You, mister or misses geneticist should be all too aware of this and appreciate its significance too.

Synthetic biologist Hamilton Smith wants to find the smallest genome that will keep a bacterium alive – and tidy up evolution’s sloppy work.

You helped make the first synthetic cell, using an artificial version of the genome of the bacterium Mycoplasma mycoides. What are you doing with it?
Our goal is to throw away everything except the core genes that keep the cell alive, to make a reduced cell. Our best estimate is that we will end up with about 400 to 450 genes. To that end, we divided the synthetic genome into eight pieces and from each section removed all the genes we think are non-essential. Each of those eight pieces is viable when combined with the rest of the naturally occurring genome. The question was could we combine the eight pieces, have our reduced cell and be done?

And what was the answer?
It didn’t work. But we found a number of combinations that did work. So right now we have a half-reduced genome. That grows pretty well. We’re closing in on the full answer though.

What might a reduced cell enable?
Once we have it we can build on it. The interesting part is to add genetic sequences to enable the cell to grow in different environments, make different compounds, or use photosynthesis, for example..

What else could you do with it?
There’s no question we’re going to end up with a reduced cell with several hundred genes. We don’t know the function of about 100 of those genes, so right there we’re probably going to make discoveries about what’s truly essential. The other thing we want to know is, how plastic is the cell? In other words, how much can we rearrange the genes? Evolution has sloppily put them together. A lot of the cell’s processes are scattered around. We’re putting them together into one neat form.

So you’re tidying up the genome?
We want to see how much we can make it a more understandable genome. Genes to do with translation of DNA into proteins over here, cell replication over here, transport over here.

Synthetic biology is in its infancy. What else might help usher it into the mainstream?
The automation of the chemical synthesis of DNA. That’s the next big aim. What’s going to drive synthetic biology is cheap, accurate DNA synthesis. And not just short stretches of DNA known as oligonucleotides, but possibly entire genes. If you can do that with a machine, where you just enter your DNA sequence and the next day you have a piece of DNA 10,000 bases long that you can experiment with, then that will drive the field. We have a big operation aiming to automate DNA synthesis.

How might that transform the field?
I’m sure right now many young people could think of interesting genetic material to design but it’s too expensive. If it’s cheap and easy you can just keep churning out stuff. It would become trivial to design whole genomes after a while.

Today I’m going to do things a bit differently.

Leave a Reply Cancel reply