Redefining Evolutionary Relationships

The evolutionary tree of life may undergo a makeover in the next decade or so.

In the past, the primary sources of information about the evolutionary relationships between organisms came from the fossil record or from comparative anatomy, physiology, or biochemistry. But now a new scientific field called phylogenomics (the study of the evolutionary history of organisms based on genetics) has emerged, thanks to the increased availability and cheap cost of sequencing DNA.

How does comparative DNA sequence data tell us anything? By tracing specific differences in the nucleotide sequences of the genes of closely related species, phylogeneticists can tell just how closely related two species are and when they most likely split from a common ancestor. That’s because when a mutation (a change in nucleotide sequence) occurs by random chance in a common ancestor, that mutation should still be present in all subsequent descendants of that ancestor. So when exactly the same mutation appears in the same gene in two species, the mutation most likely occurred before the two species split from a common ancestor – i.e. the two species are related to each other by a common ancestor.

The DNA sequences of a wide variety of species are now known, and more are being determined every day. We can expect challenges to the current tree of life (also called the phylogenetic tree) as the data are analyzed and debated.

Analyzing and Storing Genomics Data

In just the last 10 years, the cost of sequencing a million DNA base pairs has dropped from $10,000 to just $1. A single modern DNA sequencing machine can generate more data in a single day than could once be generated in a decade. Consequently, genomics researchers now face a looming problem, according to an article in Science - the speed and efficiency with which DNA sequence data can be produced will soon outstrip the ability of most computers to analyze and store the data! That’s right; despite huge gains in computer speed and storage capacity over the years, the computers are now lagging behind.

To combat this growing problem, bioinformatics specialists are increasingly turning to “cloud computing”, whereby data are analyzed and even stored on networks of computers off-site. But cloud computing raises complex new issues of data security, particularly when that data involves human subjects.

Perhaps if the cost of sequencing DNA continues to fall it may not even be necessary to store the data long-term; it could just be regenerated as needed.

Transgenic Chickens Resist Bird Flu

By inserting a small piece of DNA into chickens that interferes with bird flu viral replication, scientists have developed transgenic chickens that are genetically resistant to infection by the bird flu virus. The inserted DNA fragment blocks a key enzyme required by the bird flu virus for replication of its RNA. Transgenic chickens exposed directly to the deadly H5N1 bird flu virus still get the flu and die, but they don’t pass it on to other birds in the flock. From an economic point of view, losing a few chickens is a lot less damaging than having to destroy a whole flock to try to prevent the spread of the disease. Flu-resistant transgenic chickens might also reduce the risk of a bird flu pandemic among humans some day.

Flocks of transgenic flu-resistant chickens could be widely available within a couple of years. That’s IF regulators decide that they and their eggs are safe to eat, and IF the public accepts them. Both are big “IF”s.

New Uses for DNA Identification

It’s now possible to synthesize a nearly infinite number of unique DNA sequences. It’s also possible to identify the sequence of even a small sample of DNA quickly and cheaply. Taken together, these two advances are likely to lead to some interesting new uses of DNA technology.

According to an article in The New York Times, in Rotterdam, the Netherlands, police are experimenting with synthetic “DNA sprays” as a way to discourage robberies or to catch robbers of local businesses. When a store is robbed, the store clerk activates a security system that sprays the robber with a fine mist containing a unique synthetic DNA sequence as the robber departs. The system also notifies police that a robbery is in progress. Suspects who are apprehended within a certain time frame can then be tested for that specific DNA sequence.

Another idea: “DNA crayons” - each with a different DNA sequence - to mark valuable items that belong to you. Items suspected of having been stolen could then be tested and returned to their rightful owners. We’ll probably hear about other practical uses of DNA technology in the future. Have YOU got any good ideas?

Patenting Human Genes - An Update

In April of this year a U.S. District Court judge issued an order invalidating the patents on several human genes held by a company called Myriad Genetics. (See this blog, April 5, 2010.) The company promptly appealed, sending the issue to the next judicial level, the U.S. Court of Appeals.

Last month the U.S. Department of Justice filed a friend-of-the-court brief with the Court of Appeals, supporting the position that human genes should not be patentable. In its brief the Justice Department stated that “The chemical nature of native human genes is a product of nature, and it is no less a product of nature when that structure is ‘isolated’ from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.” (The defendants in the case had tried to argue that their method of gene isolation had somehow fundamentally changed the genes, making them patentable.) However, in a bit of a compromise, the Justice Department’s brief also suggested that human DNA that is altered in some way (i.e. is not the original human gene sequence) could still be patented.

The U.S. Patent and Trademark Office has been issuing patents for human genes for years, but the legality of the patents has never been challenged in court. The outcome of the court case could affect the commercial use of numerous human genes and gene products. For now, we await the decision of the U.S. Court of Appeals.

Familial DNA Searches

DNA testing is a modern way to positively match DNA left at a crime scene to a suspect. But what if police have DNA from a crime scene but no suspect? Most states have DNA banks only of convicted felons already in prison, so a criminal with no prior record would almost certainly go undetected.

One method being used in California is to look for partial matches between DNA from a crime scene and the state’s database of DNA from convicted criminals. A partial match, while not implicating the criminal himself, would suggest that a close relative might have carried out the crime. California used the method this month to identify a person previously convicted on a weapons charge as “probably related” to a long-sought-after Los Angeles serial killer known as the Grim Sleeper. The person’s father eventually was arrested and charged with ten murders.

This is new ethical ground for us all. As a society we need to understand the costs vs. benefits of these types of searches. The benefits are obvious – another killer identified. But the costs will be freedom lost – the freedom, for example, not to be put under suspicion and investigated for a crime unless there is reason to suspect you of an offense. Suspicion of relatives based on partial DNA matches is likely to fall disproportionately on African Americans, since they already represent a disproportionate fraction of the prison population.

Because of these concerns, California wisely put some safeguards in place for familial DNA searches. Currently, such searches require that all other investigative leads have been exhausted, that the crime is murder or rape, and that the criminal is still committing crimes – i.e. is still a threat to society. Other states considering familial DNA searches should consider similar safeguards.

Cotton Pests Infest GM Cotton

It was bound to happen, given enough time. In western India, a species of cotton bollworm has now developed the ability to infest genetically modified (GM) cotton that was specifically engineered to resist bollworm infestation.

GM cotton has become increasingly popular with farmers – so popular that approximately 50% of all cotton planted worldwide is now GM cotton. The largest users (and cotton growers) are China, India, and the United States, in that order. With so much GM cotton being planted, we could have anticipated that the cotton pests would adapt eventually. But it’s surprising how quickly it happened – bollworm-resistant cotton was only first planted in India in 2002.

Realistically, we can expect the current generation of GM crops to remain useful for several more decades. In the meantime I’m sure that researchers at Monsanto will be working on new ways to thwart the pests, just as the pests will be slowly adapting. It’s just part of the ongoing battle between species for survival.

Improving Rice Yields, Feeding the World

Two groups of scientists working independently have identified a variant of a gene in rice that can increase rice crop yields by 10%, according to a news report in Science. Neither group knew of the other’s work until their work was near completion, but when they learned of each other’s work they agreed to publish simultaneously.

Rice is a staple of a large fraction of the world’s population. Breakthroughs such as this one will help improve crop yields and feed the still-rising world population. They’re made possible by modern DNA technology and genetic engineering – techniques that allow crop scientists to sequence genomes, identify specific genes with specific actions, and then splice the genes into other plants of interest.

That's One Small Step for Gene Therapy...

French researchers report that they have successfully used gene therapy to treat beta-thalassemia in a 19-year-old male patient. Beta-thalassemia is a genetic blood disorder in which a defect in the gene coding for the beta-globin chain of hemoglobin results in persistent and life-threatening anemia and dangerously high blood iron levels. Two years after the treatment, according to the researchers, the young man no longer needs regular monthly blood transfusions and appears to be in good health.

The French team has the approval of French authorities to treat more patients with the same inherited disorder. The hope is that someday they’ll be able to successfully treat one of the most common of all genetic blood disorders – sickle cell anemia.

FDA Approves a Genetically Engineered Drug

The first human drug produced by livestock genetically engineered to contain a human gene has now been approved by the Food and Drug Administration. A company called GTC Biotherapeutics developed a herd of goats (Figure 20.10 of Human Biology) that contain the human gene for antithrombin III, a protein used to prevent blood clots in people with hereditary antithrombin deficiency. One advantage of using farm animals is that larger quantities of human proteins can be obtained from the milk of genetically engineered animals than from human blood. One of GTC’s goats, for example, can produce as much antithrombin/year as the amount that can be extracted from 10,000 gallons of human blood!

How did GTC manage to get the antithrombin to be produced in milk, so they could harvest the protein by milking the goats instead of bleeding them? Simple concept, really - they linked the human gene for antithrombin to a goat gene for a milk protein.

Detecting Protein Markers of Disease

Certain diseases are characterized as having specific abnormal proteins circulating in their blood. These proteins could serve as markers of the presence of the disease. However, the current clinical laboratory tests for these proteins are expensive, making screening millions of people for these diseases impractical. Generally, the only people who are tested are those who are at risk or who are already suspected of having the disease.

A technique just now being developed would make testing for the presence of abnormal plasma proteins easy, quick and cheap. The technique is based on glass and plastic microfluidic chips that can test for dozens of proteins in a single drop of blood, in just minutes, for pennies per test. The new technique is described in the Dec. 19 issue of Science.

Whatever Happened to Golden Rice?

Golden rice was once heralded as a cure for vitamin A deficiency, which kills or blinds children in poorer countries worldwide. But twelve years after its development golden rice is still not being produced and distributed. The primary reason is categorical opposition to all genetically engineered (GE) foods by organizations such as Greenpeace. Greenpeace argues that although golden rice might indeed benefit vitamin-deficient children, acceptance of golden rice would open the door to other GE crops that Greenpeace vehemently opposes.

In the face of intense, well-organized opposition, government regulatory agencies have been reluctant to approve GE crops, including golden rice. The company holding the patent on golden rice eventually gave up, saying there was no money in it. It's still being studied in a few labs by humanitarian organizations such as World Food Day, but don’t expect to see it on grocery shelves any time soon. That's too bad, for golden rice really is a product that could help people in need, as opposed to just helping food producers and manufacturers.

Testing Fingerprints for Illicit Substances

Could your fingerprints tell more about you than just who you are? A brief report in Science this month describes a technique that could allow crime investigators or even employers to analyze fingerprints for a variety of chemicals, including explosives and substances of abuse, such as cocaine. And since the chemicals would be determined from a single fingerprint, there would be no doubt as to who had handled the substances.

Law enforcement officials and crime investigators will welcome the technique as another weapon in their arsenal against crime. But the ability to test fingerprints for certain chemicals could also raise some privacy concerns for us all. Would we consider it ethical for an employer to enter workers’ offices to check for fingerprints containing traces of illegal drugs, without the employee’s knowledge or consent?

Reference: “Latent Fingerprint Chemical Imaging by Mass Spectrometry”. Science 321:805, August 8, 2008.

Human Drugs From Plants

Remember Cerezyme, that very expensive drug that can cost patients up to $300,000 per year? (See this blog, March 17, 2008.) Cerezyme is a human enzyme called glucocerebrosidase. It is missing in patients with a rare genetic disorder called Gaucher’s disease, found mainly in persons of Ashkenazi Jewish descent.

There may be good news for Gaucher’s disease sufferers soon. An Israeli company named Protalix Biotherapeutics has developed a protocol for producing recombinant glucocerebrosidase cheaply in large amounts. But they’re not using animals – they’re using genetically engineered carrot cells grown in cell culture in big plastic bags. The enzyme is already in Phase III clinical trials, meaning that it is being tested in human patients. If approved by the FDA it will be the first plant-made recombinant drug ever approved for use in human patients. This could be a breakthrough that leads to a whole new field in drug development – making drugs by inserting human genes into plant cells.

To read more about it and see a photo of the carrot cells in culture, go to Protalix’s website at www.protalix.com.

Pet Cloning Goes Commercial

A California biotech company called BioArts plans to hold a public auction to clone five dogs. The scientist involved in the actual cloning will be the South Korean researcher who cloned Snuppy, the male Afghan hound pictured in Human Biology, 5th ed. (p. 418), and who later claimed (fraudulently) to have cloned human embryos.

The auction will be held July 5th through 9th online, with bidding to start at $100,000. The company promises the buyer a puppy that resembles the original dog, guaranteed healthy for a year. The company says that the success rate with cloning dogs has improved to the point that 25% of all embryo transfers now result in a puppy, and that the puppy survival rate is 80%.

Human cloning can’t be far behind. The sticking point is the success rate and the health of the clone – do we really think that a survival rate on the order of 80% would be worth the risk? No one knows the long-term health risks.

How Do RNA Interference Drugs Work?

A new drug discovery field called RNA interference is hot, hot, hot these days. According to current theory, small snippets of RNA with just the right sequence should be able to interfere with the expression (translation) of genes with the corresponding complementary nucleotide sequence. Drug companies are racing to find the RNA sequences that would inactivate specific disease-causing genes. Presumably the therapeutic effect would be highly specific, since only certain genes would be inactivated.

But is that how the RNA interference drugs currently under development actually work? New evidence just published online in Nature on March 26 (doi:10.1038/nature06783) suggests that the drugs may be working by a much more general mechanism – activation of the immune system. If so, the drugs may have side effects that have not yet been considered. The findings were such a surprise that the stock prices of small companies working on RNA interference drugs went down briefly.

The Nature article is for experts only. For students, I suggest the more general New York Times article published online on Apr. 2 (“Study is Setback for Some RNA-Based Drugs”, http://nytimes.com/2008/04/02/business/02place.html).

Creating Synthetic Life

Scientists at the J. Craig Venter Institute in Rockville, Md. have succeeded in synthesizing the entire genome of the bacterium Mycoplasma genitalium, using only the four nucleotides of which all DNA is comprised. It’s an astonishing feat, considering that the M. genitalium genome is nearly 600,000 base pairs long. The next step, say the researchers, is to insert the synthetic DNA into a cell. If all goes well, the DNA will replicate itself and the cell will divide, becoming the first living, self-reproducing organism ever created synthetically in a laboratory.

The synthesis of the entire genome of an organism paves the way for experiments to determine the minimum number of genes required for life – the minimum operating system, so to speak. Looking further to the future, someday it may even be possible to create synthetic organisms for specific purposes, such as manufacturing medicines or cleaning up the environment. We’d better start thinking about how we want to regulate or control this new technology.

DNA Evidence Exonerates the Innocent

More than 300 persons convicted of rape or murder between 1989 and 2003 were later exonerated by new DNA or other evidence that proved their innocence, according to a study by a University of Michigan Law School professor (Samuel R. Gross, et. al. Exonerations in the United States 1989-2003. Journal of Criminal Law & Criminology 95:523-560, 2005.) In most cases their wrongful convictions were at least partially due to false identification by eyewitnesses. How many persons were erroneously convicted or even put to death in the past? We may never know.

The certain knowledge (with the help of DNA evidence) that mistakes were made in the past is fueling widespread reform of our criminal justice system, and thousands of innocent convicts may have their second day in court as a result. Its also prompting legal changes, including requirements in many states that confessions be recorded (to reduce the number of false confessions), and that informants’ testimony be corroborated before it can be used in a courtroom. States are also tightening up their procedures for how witnesses identify suspects in lineups and in photos.

On page 468 of Human Biology 5th ed. I describe the scientific basis for how a DNA sample is used to identify a particular individual. It's nice to see that its being used to protect the innocent, as well as convict the guilty.