By Rob DeSalle

Our ability to go back in time, so to speak, using genetic techniques is hardly a new endeavor.  The first ancient DNA isolated and analyzed was from the Tasmanian Wolf - extinct for over 100 years - using tried and true DNA cloning methods in the early 1980's. When the Polymerase Chain Reaction (PCR) was invented in the mid 1980's, the hunt was on for older and older sources of DNA. It is safe to say, though, that tissue from any long dead organism will have DNA that is badly degraded and in extremely low concentration. PCR was recognized as the best technique to overcome these technical difficulties and subsequently became the method of choice for examining long dead specimens. The same reasoning is used when forensic samples are worked with. But just as contamination is a big problem to be dealt with when working with forensics, so it is with long dead specimens.

Reports of isolation of DNA from amber-preserved plants and insects older than 100 million years began to appear. These claims were shortly rebutted based on extrapolation studies of the degradation of nucleic acids. Specifically, researchers such as Tomas Lindahl suggested that no DNA fragments longer than 1 residue would be left after 30,000 years after death (Lindahl's Line) of an organism. Since Lindahl's Line was established, few studies have attempted to go much beyond that age when working with ancient specimens. Instead, there has been a steady stream of research papers on museum specimens and recently extinct organisms. In addition, some paleo-anthropological specimens and mammal and bird subfossils (the remains of organisms that have not yet been mineralized) have been used to obtain information from long dead organisms.

With the development of next generation sequencing methods such as the 454 method (the approach used to sequence James Watson's genome) and Solexa sequencing, it was recognized that these approaches are even better suited for ancient DNA. Why?  Because the length of the sequence reads are of the order of the length of badly degraded DNA fragments found in old tissues.  Most degraded DNA will be on the order of 100 bases and the next gen sequencing approaches target fragments of about this size.  One of the more interesting and more visible organisms that has been examined in this way is Homo neanderthalensis, our closest extinct relative (there are some who feel H. florisensis, the Hobbit, is our closest extinct relative, but that's another story).  Currently, according to Svante Paabo and his group at the Max Planck Institute in Germany, is about 63% complete and should be finished by the end of this year.

However a problem arises with sequencing ancient tissue using next gen methods and it is related to the contamination of the long dead specimens with bacteria, molds and the DNA of well meaning researchers. Often times what is obtained when sequencing DNA from long dead tissue is a mix of "authentic" DNA and contaminant DNA.  The first sequences from the Neanderthal genome using next gen sequencing approaches are a sobering example of this phenomenon where it was estimated that 70 to 80 percent of the sequences came from contamination. More recent work by the groups sequencing the Neanderthal genome have improved this contamination problem to about 3%. 

Nonetheless, the potential for obtaining DNA sequences from a wide array of extinct and rare organisms is approaching reality.  How does this affect the way geneticists do research? Some very reasonable uses for analysis of ancient DNA do exist.  Analysis of extinct organisms or extirpated populations gives conservation geneticists benchmarks for how variable populations were in the past. Such information is important for a couple of reasons.  First, such measures tell us something about the natural state of things and we can guage current population genetic measures with undisturbed measures.  Such benchmarks assist conservation geneticists in making recommendations about how to conserve and manage populations of endangered species. Second, any genetic information on extirpated populations tells the conservation geneticist which genotypes are the most appropriate for reintroduction.  On the purely research side of things, knowing which genes are involved in the differences between extinct species and living ones gives the researcher an unprecedented window on evolution. A good example of this importance brings us back to Neanderthals.  Any information on what made these extinct humans like us or different from us would be incredibly interesting, and the Neanderthal genome sequences promise to give us some of that information. 

On the other hand some extremely silly things come up, such as the suggestion that a Neanderthal or a dinosaur might be resurrected using the whole genome sequences obtained from genome projects.  George Church of the Harvard Medical School suggests that, once obtained, the entire Neanderthal genome could be inserted into a chimp egg and allowed to develop in a surrogate chimp mother. Why a chimp mother? To avoid ethical problems, according to Church. That seems silly, as the ethical problems don't just start with which egg or which surrogate is used, but actually with the reason why the experiment would be done in the first place. 

Resurrecting a Neanderthal conjures up what I call the Jurassic Park Distraction, only it hits a bit closer to home. When the Jurassic Park books and movies first came out and when scientists first published claims of isolating DNA from amber preserved insects, the public response was to ask immediately: will we be able to resurrect a dinosaur? Little thought was given about why it might be useful in a scientific context or about the ethics involved. One of the reasons people would want to clone a dinosaur or a Neanderthal is just to see one with their own eyes.

Scientists have found excellent uses for using long dead tissues as sources of information, but those using the approaches should be careful about how they convey the uses to the general public. It is a disservice to the public if the ethical ramifications of the work are not made clear, and an equal disservice not to explain to the public the real scientific utility of an approach.


Rob DeSalle, Ph.D., is a curator in the American Museum of Natural History's Division of Invertebrate Zoology and co-director of its molecular laboratories.

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