## Friday, June 27, 2014

### The human machine: obsolete componenets

The previous post in this series can be found here.

In my last post in this series I described some of the ways in which gene therapy is beginning to help in the treatment of genetic disorders. A caveat of this (which was discussed further in the comments section of that post) is that currently available gene therapies do not remove the genetic disorder from the germline cells (i.e. sperm or eggs) of the patient and so do not protect that person's children against inheriting the disease. This could be a problem in the long run as it may allow genetic disorders to become more common within the population. The reason for this is that natural selection would normally remove these faulty genes from the gene pool as their carriers would be less likely to survive and reproduce. If we remove this selection pressure by treating carriers so that they no longer die young, then the faulty gene can spread more widely through the population. If something then happened to disrupt the supply to gene therapeutics - conflict, disaster, etc. - then a larger number of people would be adversely affected and could even die.

Although this is a significant problem to be considered, it is one that is fairly simply avoidable by screening or treating the germline cells of people undergoing gene therapy in order to remove the faulty genes from the gene pool. This is currently beyond our resources on a large scale, but will almost certainly become standard practice in the future.

All of this got me thinking: are there any other genes that might be becoming more or less prevalent in the population as a result of medical science and/or civilisation in general? If so, can we prevent/encourage/direct this process and at what point do we draw the line between this and full-blown genetic engineering of human populations? This is the subject of this post, but before we get into this, I want to first give a little extra detail about how evolution works on a genetic scale.

Imperfect copies

Evolution by natural selection, as I'm sure you're aware, is simply the selection of traits within organisms based on the way in which those traits affect that organism's fitness. An organism with an advantageous trait is more likely to survive and reproduce and so that trait becomes more and more common within the population. Conversely, traits that disadvantage the organism are quickly lost through negative selection as the organism is less likely to reproduce. The strength  of selection in each case is linked to how strongly positive or negative that trait is - i.e. a mutation that reduces an animal's strength by 5% might be lost only slowly from a population, whereas one that reduces it by 90% will probably not make it past one generation. In turn, the strength of that trait is determined by the precise genetic change that has occurred to generate it.

## Monday, May 5, 2014

### The human machine: replacing damaged components

The previous post in this series can be found here.

The major theme of my 'human machine' series of posts has been that we are, as the name suggests, machines; explicable in basic mechanical terms. Sure, we are incredibly sophisticated biological machines, but machines nonetheless. So, like any machine, there is theoretically nothing stopping us from being able to play about with our fundamental components to suit our own ends. This is the oft feared spectre of 'genetic modification' that has been trotted out in countless works of science fiction, inexorably linked to concepts of eugenics and Frankenstein-style abominations. Clearly genetic modification of both humans and other organisms is closely tied to issues of ethics, and biosafety, and must obviously continue to be thoroughly debated and assessed at all stages, but in principle there is no mechanistic difference between human-driven genetic modification and the mutations that arise spontaneously in nature. The benefit of human-driven modification, however, is that it has foresight and purpose, unlike the randomness of nature. As long as that purpose is for a common good and is morally defensible, then in my eyes such intervention is a good thing.

One fairly obvious beneficial outcome of genetic modification is in the curing of various genetic disorders. Many human diseases are the result of defective genes that can manifest symptoms at varying times of life. Some genetic disorders are the result of mutations that cause a defect in a product protein, others are the complete loss of a gene, and some are caused by abnormal levels of gene activity - either too much or too little.  A potential means to cure such disorders is to correct the problematic gene within all of the affected tissue. The most efficient means to do that would be to correct it very early in development, since if you corrected it in the initial embryo then it would be retained in all of the cells that subsequently develop from that embryo. This is currently way beyond our technical limitations for several reasons. Firstly, we don't routinely screen embryos for genetic abnormalities and so don't know which ones might need treatment. Secondly, the margin for error in this kind of gene therapy is incredibly narrow as you have to ensure that every single cell that the person has for the rest of their life will not be adversely affected by what you do to the embryonic cells in this early stage - we're not there yet. Thirdly, our genetic technology is not yet sophisticated enough to allow us to remove a damaged gene and replace it with a healthy one in an already growing embryo - the best we can do it stick in the healthy gene alongside the defective one and hope it does the job. There is certainly no fundamental reason why our technology could not one day reach the stage where this kind of procedure is feasible, but we are a long way off yet.

So, for the time being what can we do? Well instead of treating the body at the embryonic stage, the next best approach is to treat specifically the affected cells later on in life.  This involves identifying the problematic gene and then using a delivery method to insert the correct gene into whatever tissues manifest the disease, preferably permanently. This is broadly known as gene therapy, and is one of the most promising current fields of 'personalised' medicine.

## Thursday, March 27, 2014

### A new cosmological coincidence problem?

One of the consequences of the BICEP2 data from last week, should it hold up to scrutiny, and be seen by other experiments (I hope it holds up to scrutiny and is seen by other experiments), is that there is a significant lack of "power" in the temperature anisotropies on large angular scales.

What that sentence means is that when you look at the CMB in very large patches on the sky (about the size of the moon and bigger) its temperature fluctuates from patch to patch less than we would expect.

This was already somewhat the case before the BICEP2 discovery, but BICEP2 made it much more significant. The reason for this will hopefully turn into a post of its own one day, but, essentially, the primordial gravitational waves that BICEP2 has hopefully discovered would themselves have seeded temperature anisotropies on these large angular scales. Previously, we could just assume that the primordial gravitational waves had a really small amplitude and thus didn't affect the temperature much at all. Now, however, it seems like they might be quite large and therefore, this apparent lack of power becomes much more pertinent.

That's all fine and is something that any model of inflation that hopes to explain the origin of these gravitational waves will need to explain, despite what many cosmologists already writing papers on the ArXiv seem to want to believe (links withheld). As a side, ever-so-slightly-frustrated, note, the only papers I've seen that have actually analysed the data, rather than repeating old claims, have confirmed this problem that was clear from, at the latest, the day after the announcement.

But why does it imply a "cosmological coincidence problem"? And why is it a new coincidence problem? What's the old one?

## Monday, March 24, 2014

### The human machine: finely-tuned sensors

The previous post in this series can be found here.

All good machines need sensors, and we are no different. Everyone is familiar with the five classic senses of sight, smell, touch, taste, and hearing, but we often forget just how amazingly finely tuned these senses are, and many people have little appreciation of just how complex the biology behind each sense is. In this week's post, I hope to give you an understanding of how one of our senses, smell, functions and how, in light of recent evidence, is far more sensitive than we previously thought.

Microscopic sensors

The olfactory system is an extremely complex one, but it is built up from fairly simple base units. The sense of smell is of course located in the nose, but more specifically it is a patch of tissue approximately 3 square centimetres in size at the roof of the nasal cavity that is responsible for all of the olfactory ability in humans. This is known as the olfactory epithelium and contains a range of cell types, the most important of which is the olfactory receptor neuron. There are roughly 40 million of these cells packed into this tiny space and their job is to bind odorant molecules and trigger neuronal signals up to the brain to let it know which odorants they've detected. They achieve this using a subset of a huge family of receptors that I've written about before, the G protein-coupled receptors (GPCRs). These receptors are proteins that sit in the membranes of cells and recognise various ligands (i.e. molecules for which they have a specific affinity) and relay that information into the cell. There are over 800 GPCRs in the human genome and they participate in a broad range of processes, from neurotransmission to inflammation, but the king of the GPCRs has to be the olfactory family, which make up over 50% of all the GPCRs in our genome.

## Wednesday, March 19, 2014

### Preliminary: Cosmological impacts of BICEP2 + Planck

If anybody is interested, I'm currently drip-tweeting some of the constraints one can obtain from considering Planck and BICEP2 data together. BICEP2 did do a bit of this in their paper, but they only considered specific scenarios. They were also often a bit coy about the implications of the combined analysis. I'll try not to be ;-).

The results should only be seen as indicative, these aren't published, and never will be in this form (maybe they could be cited if used in a paper though!). They were provided to me by Sussex Uni's resident obtaining-cosmology-from-the-CMB expert Antony Lewis, after a hurried Tuesday adding the BICEP2 data to the Planck cosmology pipeline (i.e. CosmoMC) and may contain mistakes.

Antony has himself also made some of these results public at the Cosmo Coffee website.

Questions here, or on Twitter are most welcome. If you want to see specific cosmologies, I'll do my best to show them (if I have them), or ask Antony very nicely to provide them (no guarantees, of course).

You can find my Twitter account here: @just_shaun. Feel free to share!

## Friday, March 14, 2014

### "A major discovery", BICEP2 and B-modes

[Added note (on Monday): Well, wow, the rumours were, if anything, understated. I'm happy to go on record that, unless a mistake has been made, this is the greatest scientific discovery of the 21st century, and may remain so even once the century is over. I (and others) will write many more detailed summaries of what was observed over time, but BICEP2 have announced a discovery of primordial B-modes, which is extremely strong evidence of cosmological inflation (if it turns out to be scale invariant, inflation is as true as most accepted science). Matt Strassler has a good hastily written summary here. As does Liam McAllister at Lubos Motl's blog, here. Of course, this is just one experiment and maybe they've made a mistake, but the results look very robust at the moment.

Congratulations on being alive today readers! We just learned about how particles work at energies $$10^{13}$$ times greater than even the LHC can probe, and about what was happening at a time much, much less than a nanosecond after the beginning of the Big Bang.]

............................................

[Added note (on Sunday): It seems highly probable that these rumours are essentially true. Although the precise details of the results aren't yet public, the BICEP2 PI, John Kovac, has sent a widely distributed email with the following information: Data and scientific papers with results from the BICEP2 experiment will go public and be viewable here at 2:45pm GMT on Monday. At the same time a technical webcast will begin at this address.

It's going to be an exciting day!]

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The cosmology rumour mill exploded today. Harvard Astrophysics have issued a press release stating that, on Monday, they will announce a "major discovery".

This is the only hard-evidence of anything interesting on the way and it could be an announcement of anything that fits under the label of "astrophysics". This is important to keep in mind. However, for one reason or another (that is hard to nail down), cosmologists are suggesting that it is going to be about cosmology. The speculation is that it will be about the BICEP2 experiment, which has been measuring the polarisation in the CMB. The speculation is that BICEP2 have seen primordial "B-mode" polarisation.

If this speculation is true, this would be a result immense in its significance.

Primordial B-modes would be a smoking gun signal of primordial gravitational waves. This, alone, makes such a discovery important. Gravitational waves have not yet been observed, but are a prediction from general relativity. Therefore, such a discovery would be on the same level of significance as the discovery of the Higgs particle. We were almost certain it would be there, but it is good to finally see it.

However, the potential significance of such a result goes further because these primordial gravitational waves would need a source. The theory of cosmological inflation would/could be such a source. Inflation is a compelling theory, not without some problems, for how the universe evolved in its very earliest stages. If it occurred when the universe had a large enough temperature, it would generate primordial gravitational waves large enough to tickle the CMB enough to make these B-modes visible in the polarisation. As of yet, inflation has passed quite a few observational tests, but nothing has been seen that could be described as smoking gun evidence. A spectrum of primordial gravitational waves would very nearly be such a smoking gun. If the spectrum was scale invariant (i.e. if the gravitational waves have the same amplitude on all distance scales) that would be a smoking gun for inflation and accolades, Nobel Prizes, etc, etc, would flow accordingly.

All of this is just speculation, but some of it does seem to be coming from reputable sources. And some of my colleagues have been talking about tip-offs from people who wish to remain anonymous, so I figured I'd collect all the speculation I know of here in a post (let me know if I've missed anything):

The PI of BICEP2, John Kovac, gave a talk at the annual COSMO conference last year that had some pretty ambitious claims for how sensitive BICEP2 and similar experiments were going to be, so... well... we'll know on Monday. It should also be noted that, although the existence of these gravitational waves is a prediction of inflation, their amplitude is a free parameter and an amplitude this big is potentially a little surprising (for me, lower temperature inflation models just seem more compelling, others might disagree).

[Edit: The video of John Kovac's talk can be found here]

## Friday, March 7, 2014

### Quantum mechanics and the Planck-spectrum

[The following is a guest post from Bjoern Malte Schaefer. Bjoern is one of the curators of the Cosmology Question of the Week blog, which is worth checking out. This post is a historical look at some of the early parts in the history of quantum mechanics, in particular, the black-body spectrum. Questions are welcome and I'll make sure he sees any of them. Image captions (and hyper-links, in this case) are, as usual, by me, because guest posters don't ever seem to provide their own.]

Two unusual systems

Quantum mechanics surprises with the statement that the microscopic world works very differently from the macroscopic world. Therefore, it took a while until quantum mechanics was formally established as the theory of the microworld. In particular, despite the fact that two of the natural systems on which theories of quantum mechanics could initially be tested were very simple, even from the point of view of the physicists of the time, one needed to introduce a number of novel concepts for their description. These two physical systems were the hydrogen atom and the spectrum of a thermal radiation source. The hydrogen atom was the lightest of all atoms with the most simply structured spectrum. It exhibited many regularities involving rational numbers relating its discrete energy levels. It could only be ionised once implying that it had only a single electron and from these reasons it was the obvious test case for any theory of mechanics in the quantum regime. Werner Heisenberg was the first to be successful in solving this quantum mechanical analogue of the Kepler-problem, i.e. the equation of motion of a charge moving in a Coulomb-potential, paving the way for a systematic understanding of atomic spectra, their fine structure, the theory of chemical bonds, interactions of atoms with fields and ultimately quantum electrodynamics.

The Planck-spectrum was equally puzzling: It is the distribution of photon energies emitted from a body at thermal equilibrium and does not, in particular, require any further specification of the body apart that it should be black, meaning ideally emitting and absorbing radiation irrespective of wave length: From this point of view it is really the simplest macroscopic body one could imagine because its internal structure does not matter. In contrast to the hydrogen atom it is described with a continuous spectrum. In fact, there are at least two beautiful examples of Planck-spectra in Nature: the thermal spectrum of the Sun and the cosmic microwave background. The solution to the Planck-spectrum involves quantum mechanics, quantum statistics and relativity, and unites three of the four the great constants of Nature: the Planck-quantum h, the Boltzmann-constant $$k_B$$ and the speed of light c.

 The spectrum (basically intensity against wavelength or frequency) of the light from the sun (in yellow) and a blackbody with the same temperature (grey). I'm actually surprised by how similar they are.

Limits of the Planck-spectrum

Although criticised at the time by many physicists as phenomenological, the high energy part of the Planck-spectrum is relatively straightforward to understand, as had been realised by Wilhelm Wien: Starting with the result that photons as relativistic particles carry energies proportional to their frequency as well as momenta inversely proportional to their wave length (the constant of proportionality in both cases being the Planck-constant h), imposing isotropy of the photon momenta and assuming a thermal distribution of energies according to Boltzmann leads directly to Wien's result which is an excellent fit at high photon energies but shows discrepancies at low photon energies, implying that at low temperatures the system exhibits quantum behaviour of some type.