Cloned Human Embryo Produces Stem Cells

This is big. Researchers at Seoul National University have successfully harvested stem cells from a cloned human embryo. South Korea has trumped the U.S! This is like, well, not like anything before. It’s similar to the way Sputnik gave us a swift kick in the rear, but the Koreans are not threatening military conquest. Instead a lot of Americans are probably dismissing this as the work of godless heathens intent on sending us all to hell.

But really it proves my point that the United States is quickly losing our lead in biomedical research. This type of research is underway in this country, but without federal funding, it is severely hampered. American scientists quoted in the article state the need for a more even-headed approach to cloning and stem cell issues. That’s not going to happen with the current administration. In fact, all human cloning would be banned in this country if not for the foresight (or neglect) of the Senate. (When was the last time anyone credited legislators as having foresight?!)

I’ll say it again: This is big. Stem cells from a cloned human embryo, and the paper published in a leading peer-reviewed journal. This could be the beginning of the end.

See the Wired News article.

In Theory

I was joking around with some classmates the other day and hypothesized that a professor had engineered his E. coli to produce crack. I thought about it a little more, what would it take for a bacteria to produce cocaine?

It’s not a protein, so you can’t just clone the gene for it. There has to be some biochemical pathway to produce it, and fortunately, that pathway already exists in cocoa plants. So could you clone the genes for the enzymes in that pathway into your bacteria of choice and get coke out of it? It’s probably not that simple. There are indubitably some peculiarities in the functioning of the enzymes that will get lost in the translation from plants to bacteria. Then there’s the matter of purifying your product.

Sure, it’s theoretically possible. But it would be wise to try the idea out on something that’s not illegal.

DNA Synthesis

Along with the phage idea from a few days ago, I was thinking about how you would synthesize really big pieces of DNA with a novel sequence from scratch. Obviously we can produce oligos but it’s just not practicle (nor feasible I would think) to build really long pieces this way. I can’t remember if this is an idea i had or (more likely) something someone else came up with and I just can’t recall where I’ve seen it before.

You could synthesize a lot of oligos (maybe 20-mers) for your sequence and the complementary strand. The oligo would be designed such that the breaks in one strand fall in the middle of an oligo for the other strand, crudely diagrammed thusly:

BBBBBBBBBB BBBBBBBBBB BBBBBBBBBB
BBBBB BBBBBBBBB BBBBBBBBBB BBBBB

For best results, the gaps could even span multiple bases in the antisense strand. Mix with some PolIII and ligase, repeat until sufficiently long DNA.

Phun with Phages

I started reading this article yesterday about using bacteriophages to treat infections, especially strains that are resistent to most antibiotics. The great thing about phages is that they can be built entirely from their DNA. Cellular processes depend on having a progenitor — one cell becomes two becomes four. It’s been a very long time since nothing became one cell. But a bacteriophage is described entirely by its DNA; no other part of the virus enters the host. (Many viruses of higher organisms, HIV for instance, contain enzymes within in the virus particle that are required to complete their life cycle. Thus the entire virus must enter the host cell.)

The other exciting thing about phages is that they are lytic — they destroy their host. So I started thinking about ways to hijack their lifecycles. It’s routine to clone a gene who’s protein you’re interested in, overexpress it in E. coli and then purify the protein. But it can be tricky to get the protein out of the bacteria. Wouldn’t it be simpler if the bacteria broke open once they filled up with the protein? It seems like you could clone the protein into a phage genome and let it go to town.

That’s pretty academic, though. Consider a patient who’s got a nasty bacterial infection, one that’s resistent to antibiotics. You could attack with phage and it would be all good, but what if we could get those bacteria to produce something else while they’re being destroyed by the phages. You’d have 1% of your phages actually be pseudo-phages, virus particles that contain non-viral DNA that encodes some other product. This other product could be a painkiller or perhaps a cytokine or other compund to boost the immune system.

Tissue Engineering

I was reading this article yesterday in Wired (the part about “Regeneration”), and earlier in the week, I read about using nanotechnology in a similar fashion. In terms of fields of study, I am interested in tissue engineering as well as bioinformatics. One possible way to combine the two would be, for instance, if there was a motif that represented growth factors, you could search all the ORFs for similar motifs. I don’t know much of anything about growth factors, but this approach should work reasonably well for, say, 7TM receptors. It’s sort of “reverse proteomics.” Another technique might be to use proteomics to identify the genes for growth factors present in, for example, a developing liver. Or even if you had just one growth factor identified, you could search for similar promoter regions.

There are a couple of catches to these genomic searches. With a search for promoters, you’d have to be so many base pairs upstream from the start codon, and you’d have to incorporate a certain amount of “fuzziness” to the search. The motif search would be harder. You’d have to know which residues were important, what other amino acids could substitute, and then look for all the possible base combinations in an ORF. To some degree, it would help to know what the active site looked like, how the important residues related both three-dimensionally and in sequence, and so on. But this is something people are currently putting a lot of effort into, so you couldn’t expect a computer to do it very well at the present moment.

Genetic Knowledge

It’s my understanding that in his latest book, Stephen Wolfram asserts that humen beings are born with an understanding of physics. (I haven’t personally read the book.) I don’t think this is exactly the case. Rather, human beings are born with the capacity to understand physics, in much the same way we are born with the capacity to learn language. No one is brought into the world speaking English or Swahili, but we learn it over time. Some extreme cases of child abuse have demonstarted that if we don’t learn a language by the time puberty hits, then that capability is lost. Likewise, we all learn physics to some degree because we’re all exposed to it. A child born and raised in a zero-gravity environment would have a very different understanding of physics than her earthbound cousins.

Nonetheless, even if the knowledge itself isn’t encoded in our DNA, it is still humbling to realize that that molecule contains the power to enable us to learn. DNA is responsible for the structures that form in the brain, that then absorb experience and transform it into knowledge. This is where the size of the human genome comes into play. It seems farfectched to me to imagine that there’s a gene (or more specifically, an allele) for “physics brain structures” any more than there’s one for a dog’s olfactory lobes. It seems much more plausible that there are highly complicated mechanisms that control the development of these structures, especially in the embryo.

This idea of complex and intricate control mechanisms is borne out by the size of the human genome. It was once estimated to be 100,000 genes, but it is now thought to be closer to 30,000. Same number of base pairs, no matter what the count. All that extra data may not be just “wasted space.” Instead, perhaps it is highly complex and evolved control mechanisms, many of which function primarily (or exclusively) during embryonic development. And it is these control mechanisms that are really what separate human beings from nematodes.

Tyrosine kinases and signaling pathways are one example of a control mechanism that’s found only in higher animals. I imagine there are many many more.