Sleeping secret

A  In 1846, a Bostonian dentist called William Morton removed a tumour from the neck of a newspaper printer to whom he had administered ether. The printer felt no pain. Ever since then, doctors have been frying to fathom exactly what causes the curious state of unconsciousness, now known as anaesthesia, into which he lapsed.

B  For a long time, researchers in the field believed that anaesthetics worked by dissolving in the fatty sheaths that insulate nerves. This, it was theorized, caused them to interfere with the electrical signals that pass along those nerves. Since one of the few things that anaesthetic chemicals seemed to have in common was a tendency to dissolve in fats, and their solubility was related to their effectiveness, that hypothesis looked good until the suggested electrical effects were measured in the 1980s and discovered to be too small.

C  At around that time, however, another idea was becoming popular. This was that anaesthetics combine with critical proteins in the central nervous system and bring them — and consciousness — grinding to a halt. Subsequent research has shown that anaesthetics can, indeed, bind to protein molecules, and can sometimes affect their function as a result. But nobody has yet identified the elusive proteins involved anaesthesia. In October, however, Roderic Eckenhoff, an anaesthesiologist at the University of Pennsylvania, will publish a paper that may bring that identification closer. Though he has not found the guilty proteins, he thinks he knows something important about their characteristics, and thus how anaesthetics perform their trick.

D  Proteins consist of long chains of chemical links known as amino acids. These chains, however, are usually folded up into more or less globular shapes which are held steady by weak chemical bonds between adjacent parts of the chain.

E   Since the shape of a protein is critical to its function (particularly if it has a precisely sculpted docking port for other molecules to enter). Dr. Eckenhoff suspected that anaesthetics work by changing the stability of the folding of a particular protein, thus affecting how well that protein does its job. Anaesthetics might achieve this either by making the shape of a protein so stable taht it cannot flex in response to docking and undocking molecules, or so unstable that the docking port loses its shape. The test of this theory, to be published in October’s Molecular Pharmacology, looked at two proteins (albumin and myoglobin) which have nothing directly to do with anaesthesia, but which are easy to extract in large quantities for experiments.

F  Dr. Eckenhoff’s previous work has shown that when an anaesthetic molecule such as isoflurane binds to albumin (a component of blood), the protein becomes more settled in its folded pattern. This means that anaesthetics are less likely to stick to it if it is destabilized. By contrast he showed that myoglobin (a component of muscle) opens up and becomes less stable when it hosts a molecule of isoflurane — which means that anaesthetics are more likely to stick to it if it is destabilized.

G  Since it is one of the characteristics of anaesthesia that its effectiveness weakens with temperature and pressure. Dr. Eckenhoff wanted to examine the effects of these two variables on the proteins in question. Raising the temperature destabilized both proteins (no great suprise, given that molecules, shake more when they are hotter). So did increasing the pressure. But Dr. Eckenhoff was able to measure the precise amount of destabilization by carrying the experiments out in water containing a radioactive form of hydrogen called tritium.

H  In the normal course of events, a protein molecule will swap hydrogen atoms with the surrounding water from time to time — and if that molecule has been partially unfolded, there will be more hydrogen available to swap, since atoms on the inside as well as the outside of the globule will be available for exchange. The extent to which a protein has been destabilized can, therefore, be measured by how radioactive it becomes in a given period of time.

I  The stability curves for an albumin at different temperatures and pressures turn out to have the same sort of shape as the curves for the effectiveness of anaesthetics (those of myoglobin do not match at all). And two other lines of evidence from the paper also indicate that the proteins involved in anaesthesia have albumin-like qualities.

J  One is that only albumin responds to changes in the concentration of isoflurane in the way that would be predicted if it were acting like a protein responding to anaesthesia. The other is the response of albumin to different forms of isoflurane.

K  The isoflurane molecule comes in two varieties, which are mirror images of each other. For most chemical purposes the varieties are identical, but anaesthesia can tell the difference — and one is more potent than the other. Dr. Eckenhoff has found that the more potent variety binds more strongly to albumin, but not to myoglobin.

L  Anaesthesia, therefore, seems to work by stabilizing rather than destabilizing critical proteins. But which ones? The most likely candidates are the protein receptors of the small chemical messengers (known as neurotransmitters) which carry signals from one nerve cell to another at special sites called synapses. Work on glutamate receptors, which are responsible for simulating the brain, suggests that these are, indeed, inhibited by anaesthetics. But in contrast to this, John Mihic of the University of Colorado and his colleagues have recently made a case for anaesthetics working by increasing rather than decreasing the effects of receptor molecules — in this case the receptors for GABA and glycine, two neurotransmitters that calm down excited synapses. How that fits in with the Eckenhoff model remains to be seen. Clearly, however, anaesthesia has not given up all of its secrets yet.

The above reading passage has twelve paragraphs A – L. Choose the most suitable headings for paragraphs B – L from the list of headings below. Write the appropriate numbers (1-14) in the spaces provided.
NB: There are more headings than the paragraphs so you will not use all of them. You may use any of the headings more than once.

List of headings
1. Proteins might play a part in anaesthesia2. How to measure a protein’s destabilization 3. A hypothesis held before the 1980s 4. Findings made by Dr. Eckenhoff 5. Different potency of isofluranes’ two varieties 6. The proteins have albumin-like qualities 7. Shapes of proteins	8. How anaesthesia works – still a puzzle 9. The two evidences showing the proteins’ albumin-like quality 10. Effect of the two variables on proteins 11. Anaesthetics and insomnia 12. Two conflicting theories 13. Dr. Eckenhoff’s theory14. Ill effects of anaesthesia

 Đáp án: A.8; B.3; C.1; D.7; E.8; F.4; G.10; H.2; J.6; K.5;L.12