BioScience Biz

Who's your mama? (by Steven S. Clark)

Remember Jurassic Park—the Steven Spielberg sci fi flick in which a greedy businessman and his mad-scientist minions reached inside prehistoric amber to extract, and ultimately clone, dino DNA that had been sucked up by a sap-trapped bug? Seem far fetched?

Maybe not so much.

An international team of scientists from Germany, the US, Croatia and Finland just reported in the prestigious journal, Cell, that they had cloned and sequenced the Neanderthal mitochondrial genome. The DNA was isolated from a 38 thousand-year old fossilized leg-bone that was found in the Vindija Cave in Croatia in 1980.

Mitochondria are small bacteria-like structures found inside cells where they function as the cell’s powerhouse—they produce chemical energy that the cell uses to drive its biology. The relevant thing here is that mitochondria contain their own small, characteristic genome that is distinct from, and inherited differently than, the much larger genome in the cell nucleus. In your prototypical maternal/paternal genetic inheritance, a sperm fertilizes an egg and the nucleus of each contains one-half of the genome the embryo will need to function. Upon fusion of the two nuclei, the fertilized egg, called a zygote, acquires the full genome that it needs to function and grow.

In contrast to the inheritance of the nuclear genome from both parents, the mitochondrial genome is solely obtained from the mother. When a tiny sperm, that is not much more than a nucleus with a tail, fuses with the much larger egg cell, the subcellular organelles of the egg provide the necessary machinery to allow the zygote to survive, divide and do its thing. Hence, the zygote’s mitochondria are completely inherited from the mother. This means that by tracking lineage relationships through mitochondrial DNA (mtDNA) sequence analysis one is examining matrilineal descent between different biological species, genera and families. It is a lens into our past to Eve—the mother of us all.

This amazing feat of cloning and sequencing prehistoric DNA entailed careful and painstaking sterilization of the specimen and then, in a sterile room, carefully chipping away the mineralized bone’s surface to uncover small amounts of DNA that had been sequestered within the stone bone.

High tech DNA cloning and sequencing methods were used to unravel a DNA sequence that clearly came from mitochondrial DNA, but whose? Since we don’t have Neanderthals walking around today—no, not even the Troglodytes in Congress—how could the investigators be sure that the DNA was in fact from the bone’s original owner and not from say, the saber tooth tiger that gnawed on it eons ago or even from some plant matter that was trapped in the sediment that encased and fossilized the bone?

Fortunately, scientists have an extensive database of mtDNA sequences from extant humans as well as from many old and new world apes and other non-hominid animals for comparison. Comparing the Neanderthal DNA to this database revealed that the mtDNA clearly had a hominid origin, but was not from any known family of primates. This confers a high degree of certainty that the DNA was indeed from the fossil bone—the scientists were peering through a molecular window into the genetic history of a species that first appeared pre-history!

The first Neanderthal fossil was found in the Neander Valley near present-day Düsseldorf, Germany and the fossil record indicates that they are the closest known hominid relative to humans—closer even than chimps. The DNA sequence confirms this archeological conclusion. Genetic mutations occur at a predictable rate per generation, and once fixed in a genome, are subsequently inherited by the progeny while new mutations continue to appear at the predictable rate; thus, leaving a bread-crumb-like trail to the past from whence we came. From this, one can construct a “molecular clock” with which to estimate how long ago different hominid species diverged and this indicates, with a 95% statistical certainty, that humans and Neanderthals split off from a common ancestor between 520-800 thousand years ago. In contrast, humans and chimps diverged some six million years ago. The genetic data also showed that Neanderthals likely lived in very small numbers; maybe no more than 10,000 alive at any one time; they were in a distinct minority relative to humans.

Anthropologists have long known that Neanderthals and humans overlapped in history as well as regionally, raising speculation as to whether humans and Neanderthals interbred. However, you can rest easy since the Neanderthal mitochondrial genes "were distinctly different to modern humans, suggesting Neanderthals never, or rarely, interbred with early humans." Perhaps that fact is mostly of interest to a prurient anthropologist who has been in the field too long, but it also should still the salacious speculation from the History Channel of illicit communion between the two species. In other words, Great Grandma was not one of the knuckle-draggers, regardless of uncle Ned’s jutting jaw and flat forehead—that is just the luck of the draw from the Homo sapien gene pool and not due to genetic “contamination”.

Another upshot of this study is that the lessons learned about isolating and sequencing antediluvian DNA will be useful for the analysis of the entire Neanderthal genome that will soon come.

Can "Neanderthal Park" be far behind?

For the inventor--mind your intellectual property

To disclose your idea or not to disclose it can be a critical question. The currency of success in science, especially academic science, is the almighty publication--invited talks also are highly valued.  The more we do of both, the more respect we generate among our colleagues and promotion committees. But, a scientist with an idea that might have commercial value needs to weigh the benefits against the risks of disclosing that idea, especially in published form. There can be a right and wrong time to do this.

A recent article in bioentrepreneur discusses the pros and cons of publishing as it relates to intellectual property. The insightful article talks about the use of “defensive” publication as a way to solidify patent claims. But the article also talks about the timing of disclosing a marketable idea and a researcher would be wise to consider these points.

“In the United States, when an inventor publishes his or her invention, a one-year grace period ensures that the inventor's patent rights are not immediately extinguished. Publication immediately extinguishes most non-US patent rights, however, even those of the inventor. A decision to publish is thus a decision to irreversibly surrender potential patent rights. Such an important decision should only be made in the context of a comprehensive IP strategy.”

Biotech in high school?

In the Journal of Life Sciences, award winning high school teacher, Kirk Brown, tells about how he has inspired a new generation of scientists through an unusual curriculum and partnership with industry.

Read here how Mr. Brown has created many personal success stories at a blue-collar high school in central Califorinia.  It is a story that could be repeated anywhere there is a strong biotech presence.