Rapid Genetic Testing in a Clinical Setting

For what appears to be the first time, doctors have used rapid genetic testing to immediately inform their treatment of patients. Basically, some people react poorly to a particular drug, and the genetic variant responsible for this is known. Doctors could test whether or not they had this genetic variant and administer the correct drug accordingly. The steps, as outlined in Medical Xpress:

The point-of-care genetic test used in the study is a first in medicine and overcame many of the previous obstacles that had prevented routine clinical genetic testing. The test featured:

— A saliva swab performed by clinical nurses at the bedside with no prior training in genetic laboratory techniques.
— A one-step insertion of the swab into a testing machine.
— Sixty minutes to identify whether individuals carried the at-risk genetic variant.

The Medical Xpress article goes into more detail and background, if you’re interested.

This technology sounds pretty great. How great though depends on how common this kind of situation is – how often medical care depends on genotype. I wouldn’t be surprised if I’d heard of that situation, but nothing comes to mind right now. I guess we’ll find out when we’re getting swabbed. If it is common, well, saving lots of money on healthcare would be pretty fantastic – and, of course, being in better health would be nice.

If you’re curious about DNA sequencing, you should check out this Ars Technica article that I’ve linked to before; it lays out the basics of the science well enough that I won’t try to replicate it here.


Genetic Changes in the Brain Over a Lifetime

Researchers from the Roslin Institute in Edinburgh have found that retrotransposons change the genetic structure of brain cells over time, which may be behind some neurological disorders. Retrotransposons are genes that can be multiplied and re-inserted into the genome. They can have effects on the cell if they’re inserted in or near other genes that encode proteins, since they can change how, when or if those proteins are made. Because retrotransposons can be multiplied, they make up a huge proportion of genomes – in our case, around half. 

Brain cells are probably the most interesting type of cells to study in this respect since they can generally survive for your entire lifetime, meaning that individual cells can accumulate quite a bit of genetic changes and become very genetically distinct from their neighbours. If they kept multiplying over our lifetimes like other kinds of cells, those changes would instead be passed on to new cells and the population would not end up being as different. 

From Medical Xpress:

The team, from the Roslin Institute in Edinburgh, studied the DNA structure from brain cells from three deceased people who died from non-brain related incidents and who were otherwise normal and healthy; focusing most specifically on the hippocampus and caudate nucleus. In so doing they were able to identify 25,000 areas where there was evidence that retrotransposons had inserted themselves. In addition, they found evidence of three distinct families of retrotransposons, one of which, the Alu family, had never before been seen in the brain…

They also found that they copied themselves into the genetic material in cells that make up some of the most important parts of the brain, such as chemical transporters. Also notably, some were found in the genes in some cells that are known to fight tumor growth, leading to speculation that they might in fact contribute to certain types of brain cancers. Adding fuel to that fire were retrotransposons found in cells that regulate proteins in the brain which of course have been linked to all manner of psychiatric ailments such as schizophrenia.

They also found a lot more copying went on in the hippocampus then in the caudate nucleus, something that could lead to speculation regarding the nature of memory and learning in general if the cells in that part of the brain have individualized DNA structures.

Genetics and neurobiology are both relatively new fields, so there have been and will be pretty awesome breakthroughs in both, of which this seems to be one. Things always end up being way more complicated than we thought, but these are also great opportunities for breakthroughs in medicine and technology. I look forward to seeing how this changes the field. 

The BBC also has an article on this, out of which I’d like to share just one gem:

They say their discovery completely overturns previous theories about how the brain works.

Wow. I guess we can throw out our biology textbooks then.

One would hope that this huge claim was put into some kind of context, but it wasn’t. This is a really silly statement that I would hope is a misrepresentation of what the authors actually may have said. This is why it’s generally better to read science news websites like PhysOrg or ScienceDaily than to read newspapers’ science sections, if you’re willing to wade deeper into science. 

The Science of Cloning

LiveScience has a good FAQ article on the basics of how animals are cloned. Cloning is only going to get more prominent in the future, so it wouldn’t hurt to have an idea of what it is and how it’s done. I won’t summarize it here, since it’s already explained briefly and nicely. The last paragraph mentions the recent successful cloning of a human embryo for harvesting embryonic stem cells, which I discussed a while ago along with some background on stem cells.

As always, feel free to let me know if you’d like any aspect explained in more detail.

A Mechanical DNA Clock Determines Embryos’ Segmentation

Researchers have discovered a mechanism for how animal embryos segment themselves (roughly from head to tail) with extreme precision and consistent timing: the DNA responsible for determining the fate of different segments unravels in the same order and with the same timing as the segmentation itself. Remember that DNA is generally twisted and looped up as tightly as possible, so that molecules that could span 6 feet end-to-end are crammed up into a few nanometres; specific DNA sequences get unwound when they’re needed so that they can be read and transcribed by proteins, and then have an effect on the cell. 

From Science Daily:

During the development of an embryo, everything happens at a specific moment. In about 48 hours, it will grow from the top to the bottom, one slice at a time — scientists call this the embryo’s segmentation. “We’re made up of thirty-odd horizontal slices,” explains Denis Duboule, a professor at EPFL and Unige. “These slices correspond more or less to the number of vertebrae we have.”

Every hour and a half, a new segment is built. The genes corresponding to the cervical vertebrae, the thoracic vertebrae, the lumbar vertebrae and the tailbone become activated at exactly the right moment one after another… How do the genes know how to launch themselves into action in such a perfectly synchronized manner? “We assumed that the DNA played the role of a kind of clock. But we didn’t understand how.”

Very specific genes, known as “Hox,” are involved in this process. Responsible for the formation of limbs and the spinal column, they have a remarkable characteristic. “Hox genes are situated one exactly after the other on the DNA strand, in four groups. First the neck, then the thorax, then the lumbar, and so on,” explains Duboule. “This unique arrangement inevitably had to play a role.”

The process is astonishingly simple. In the embryo’s first moments, the Hox genes are dormant, packaged like a spool of wound yarn on the DNA. When the time is right, the strand begins to unwind. When the embryo begins to form the upper levels, the genes encoding the formation of cervical vertebrae come off the spool and become activated. Then it is the thoracic vertebrae’s turn, and so on down to the tailbone. The DNA strand acts a bit like an old-fashioned computer punchcard, delivering specific instructions as it progressively goes through the machine.

“A new gene comes out of the spool every ninety minutes, which corresponds to the time needed for a new layer of the embryo to be built,” explains Duboule. “It takes two days for the strand to completely unwind; this is the same time that’s needed for all the layers of the embryo to be completed.”

This system is the first “mechanical” clock ever discovered in genetics. And it explains why the system is so remarkably precise.

I wanted to share this article both because it seems like a very novel discovery and because it touches on some DNA and development fundamentals, but to be honest it’s a bit confusing to me, and I wish I could read the actual article in Science for an explanation. This article basically reads like the embryo is one cell with one set of DNA, which, unless I’m thoroughly off the mark, is not the case during segmentation, by which I’m assuming they mean somitogenesis. This begs the question: in which cells are they noticing this Hox activity? How is this pattern being communicated between cells? 

I may be missing something obvious, but I wish this Science Daily article were clearer. Anyway, in conclusion, here’s an interesting time-keeping mechanism during embryogenesis 🙂

Side note: Apologies for the gap in posts since Thursday; like I said in the previous post, I was marathon cramming for my GRE biochemistry test on Saturday, and my brain has been hibernating since then. It’s slowly recovering from the trauma. Fear not, though, we won’t miss a thing: I’ll be going through every article in my RSS feed since Thursday, all 1000+. No science will escape us!

The Science of DNA Evidence

Wired has an informative article from Ars Technica on the science behind the DNA evidence used in court, in the context of the prominent Amanda Knox case – a young American originally convicted of murder in Italy, then recently released. There are two main points: first, the DNA evidence they had against Amanda Knox was weak and wouldn’t have been considered in a U.S. court. Second is the explanation of how DNA evidence is gathered, analyzed and interpreted.

A very brief summary of the science would be that everyone has short, repeated sequences in their DNA that don’t code for anything. These are repeated to different degrees in different individuals. Seeing how many times any of these sequences repeats, across a large number of types of sequences, allows you to distinguish different individuals’ DNA.

The article goes more in-depth into the science, and links to another Ars Technica article with even more specific science behind DNA sequencing and replication, so if you’re interested at all, I encourage you to check it out. If you have any questions afterwards, I’d be happy to try to address them. 

Is a Whole Organism More Than the Sum of Its Parts?

Here is the second part of the essay series I started looking at yesterday, about the complexity of living things and ultimately pointing towards an argument for a new type of scientific explanation for life. The article is called The Unbearable Wholeness of Beings, and unfortunately it started being disagreeable to me from the get-go. If you’re interested in the idea that there may be more to life than chemical processes – whether in agreement, disagreement or uncertainty – you should check it out. 

(Update: here is my post on the third essay.)

This post is much longer than the norm – I had the “yelling at the TV” effect where I couldn’t help but disagree as I was reading along, so I thought I’d share my opinions along the way.

Animals and plants are a long way from rocks and clouds, and also from automobiles and computers. The need to point this out today is one of the startling aspects of the current scientific landscape. It is true that the concept of “vitalism” has been problematic in the history of biology, but no less so than “mechanism.” The two problems are in fact devilishly intertwined. We will never get straight about vitalism if we do not also get straight about mechanism. And until we sort through the associated confusions, we have little hope of meaningful conversation about many of the perplexities vexing biologists today…

Here, then, is my question: Are you and I machines? Are we analyzable without remainder into a collection of mechanisms whose operation can be fully explained by the causal operation of physical and chemical laws, starting from the parts and proceeding to the whole? It might seem so, judging from the insistent testimony of those whose work is to understand life.

The article goes on again into the depths of cell biology. The last article explained these complexities to show that the field of biology is not what it used to be, and that scientists have discovered that things are not as easily explained as they once thought. This article unfortunately seems to be making similar points but to the end of making a lower-level “god of the gaps” argument – not for religion, but for an explanation of life that doesn’t conform to modern science. 

The fact that I called it a god of the gaps argument shows chiefly what I think is wrong with it; it criticizes conventional explanations without offering any evidence for an alternative, and assumes that a current failure to fully comprehend something indicates a permanent failure. 

The author makes a few arguments, of which I’ll only excerpt a morsel: Read more of this post

The Complexity of Life’s Building Blocks

I just discovered a site called The New Atlantis: A Journal of Technology and Society. It features in-depth, apparently very articulate essays on science and society, which seem pretty awesome to me, although they are certainly on the long side. A recent article called “What Do Organisms Mean?” caught my eye – it seems to be a discussion of materialism, that will inevitably go into the question of what makes life “alive” – I must read it! 

It’s the third essay in a series though, so I faithfully started at the beginning, with “Getting Over the Code Delusion” (Update: my takes on the second and third essays). It discusses how the formerly popular assumption that DNA sequence determined everything about life has been changing as science delves into epigenetics (can’t seem to get away from that topic!) and the mind-boggling complexity of DNA’s structure.

… The most striking thing about the genomic revolution is that the revolution never happened. Yes, it’s been an era of the most amazing technical achievement, marked by an overwhelming flood of new data. It’s true that we are gaining, even if largely by trial and error, certain manipulative powers. But our understanding of the integrity and unified functioning of the living cell has, if anything, been more obscured than illumined by the torrent of data…

The human body is not a mere implication of clean logical code in abstract conceptual space, but rather a play of complexly shaped and intricately interacting physical substances and forces. Yet the four genetic letters, in the researcher’s mind, became curiously detached from their material matrix. In many scientific discussions it hardly would have mattered whether the letters of the “Book of Life” represented nucleotide bases or completely different molecular combinations. All that counted were certain logical correspondences between code and protein together with a few bits of regulatory logic, all buttressed by the massive weight of an unsupported assumption: somehow, by neatly executing an immaculate, computer-like DNA logic, the organism would fulfill its destiny as a living creature. The details could be worked out later.

… The central truth arising from genetic research today is that the hope of finding an adequate explanation of life in terms of inanimate, molecular-level machinery was misconceived. Just as we witness the distinctive character of life when we observe the organism as a whole, so, too, we encounter that same living character when we analyze the organism down to the level of molecules and genes. One by one every seemingly reliable and predictable “molecular mechanism” has been caught deviating from its “program” and submitting instead to the fluid life of its larger context. And chief among the deviants is that supposed First Cause, the gene itself. We are progressing into a post-genomic era — the new era of epigenetics.

The essay quickly becomes a rather detailed description of just how insanely complex DNA is, and the factors that determine how it’s read. I think it’s accessible to anyone with a basic biology background but it does get pretty heavy. If you want to feel like a genetics boss, you should dive in; a few minutes’ reading will teach you a lot, and maybe give you a good dose of humility about the organized insanity that’s going on in our cells. 

Based on this article, and Wikipedia’s description of The New Atlantis as “traditionalist conservative,” I can’t help but feel that I’ll disagree with the last essay’s conclusion – I assume, that there is something inherently unquantifiable, or supernatural, about life – but it promises to be an interesting and informative read in any case, so I’ll go on to part 2 tomorrow.

Edit: Further research has shown that the author has this to say about this series of essays:

They are attempts to describe our reigning (and mostly unconscious) cognitive habits, the limitations of conventional science, and the redirections required for a new, qualitative science. By virtue of its qualitative character, such a science will be holistic and irreducibly ethical (or unethical).

So… now I’m pretty confident that I’m going to disagree with whatever it is he concludes. But that makes it more interesting, doesn’t it? We’ll see how this goes over the next couple of days. (Update: check out my posts on the second and third essays in the series.)

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