Tag: drug

Evolution without genes – prions can evolve and adapt too

By Ed Yong | December 31, 2009 2:00 pm

If you search for decent definitions of evolution, the chances are that you’ll see genes mentioned somewhere. The American Heritage Dictionary talks about natural selection acting on “genetic variation”, Wikipedia discusses “change in the genetic material of a population… through successive generations”, and TalkOrigins talks about changes that are inherited “via the genetic material”. But, as the Year of Darwin draws to a close, a new study suggests that all of these definitions are too narrow.

Prions.jpgJiali Li from the Scripps Institute in Florida has found that prions – the infectious proteins behind mad cow disease, CJD and kuru – are capable of Darwinian evolution, all without a single strand of DNA or its sister molecule RNA.

Prions are rogue version of a protein called PrP. Like all proteins, they are made up of chains of amino acids that fold into a complex three-dimensional structure. Prions are versions of PrP that have folded incorrectly and this misfolded form, called PrPSc, is social, evangelical and murderous. It converts normal prion proteins into a likeness of its abnormal self, and it rapidly gathers together in large clumps that damage and kill surrounding tissues.

Li has found that variation can creep into populations of initially identical prions. Their amino acid sequence stays the same but their already abnormal structures become increasingly twisted. These “mutant” forms have varying degrees of success in different environments. Some do well in brain tissue; others thrive in other types of cell. In each case, natural selection culls the least successful ones. The survivors pass on their structure to the “next generation”, by altering the folds of normal prion proteins.

This process follows the principles of Darwinian evolution, the same principles that shape the genetic material of viruses, bacteria and other living things. In DNA, mutations manifest as changes in the bases that line the famous double helix. In prions, mutations are essentially different styles of molecular origami. In both cases, they are selectively inherited and they can lead to adaptations such as drug resistance. In prions, it happens in the absence of any genetic material. 

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CATEGORIZED UNDER: Evolution, Medicine & health

Rapamycin – the Easter Island drug that extends lifespan of old mice

By Ed Yong | July 8, 2009 1:00 pm

Blogging on Peer-Reviewed ResearchIt’s 1964, and a group of Canadian scientists had sailed across the Pacific to Easter Island in order to study the health of the isolated local population. Working below the gaze of the island’s famous statues, they collected a variety of soil samples and other biological material, unaware that one of these would yield an unexpected treasure. It contained a bacterium that secreted a new antibiotic, one that proved to be a potent anti-fungal chemical. The compound was named rapamycin after the traditional name of its island source – Rapa Nui.

Skip forward 35 years and rapamycin has made a stunning journey from the soil of a Pacific island to the besides of the world’s hospitals. Its ability to suppress the immune system means that it’s given to transplant patients to stop them from rejecting their organs and its ability to stop cells from dividing has formed the basis of potential anti-cancer drugs. But the chemical has an even more interesting ability and one that has only just been discovered – it can extend lifespan, at least in mice.

David Harrison, Randy Strong and Richard Miller, leading a team of 13 American scientists, have found that capsules of rapamycin can extend the lifespans of mice that eat them by 9-14%. That’s especially amazing given that the mice were already 20-months-old at the time of feeding, the equivalent in mouse years of a 60-year-old human.

There will undoubtedly be headlines that proclaim the discovery of the fountain of youth or some such, but it is absolutely critical to say up front that this is not a drug that people should be taking to extend their lives. Rapamycin has a host of side effects including, as previously mentioned, the ability to suppress the immune system. Harrison says, “It may do more harm than good, as we know neither optimal doses nor schedules of when to start for anti-ageing effects.” So the new discovery doesn’t put an anti-ageing pill within our grasp. It’s far better to see it as a gateway for understanding more about the basic biology of ageing, and for designing other chemicals that can provide the same benefits without the unwanted risky side effects.

Nonetheless, it’s still very exciting, especially since the nutrition market is already awash with supplements that claim to slow the ageing process but which have little evidence to back their claims. Likewise, scientists have tested a number of different chemicals but the few positive effects have typically been small or restricted to a specific strain of mouse. Rapamycin is different – as Harrison himself explains, “no other intervention has been this effective when starting so late in life on such a diverse population.”

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