By Justin Gillis / The Washington Post /

Saturday, December 31, 2005

WASHINGTON — Shares of the nation’s largest biotechnology companies are trading at or near record levels as the year comes to a close, a payoff for investors in companies that have been putting intensive focus on cancer and other hard-to-treat diseases over the last few years.

The American Stock Exchange biotechnology index, which tracks some of the largest companies in the industry, hit a five-year high during the trading day Tuesday, powered by optimism over recent or impending treatment approvals at the Food and Drug Administration. Shares of the industry’s bellwether company, Genentech Inc., hit their highest point ever earlier this month, though they’ve pulled back a bit since then.

Analysts said the large biotech companies, which include Genentech and a handful of other big names, such as Amgen Inc. and Gilead Sciences Inc., are beginning to replace traditional pharmaceutical stocks in the holdings of many investment funds that want a piece of the growing health care market.

The strong performance is largely confined to the high end of the biotech industry — the companies that have put blockbuster drugs on the market and have grown into vast enterprises with thousands of employees and drug factories humming night and day.

The Amex index, which tracks the performance of these companies, is up 110 percent since bottoming out in mid-2002, compared with an increase of 30 percent over the same period in the Standard & Poor’s 500-stock index. For 2005, the biotech index is up 25 percent, while the broader market, as reflected by the S&P 500, rose a mere 4 percent.

By contrast, a separate index that reflects the share prices of smaller biotech companies, the Nasdaq Biotech Index, has essentially mirrored the broader market, up about 3 percent for the year.

The traditional drug industry hit a rocky patch this year: Merck & Co., once the world’s most respected drug company, is defending itself against a slew of lawsuits claiming it hid safety problems with its Vioxx painkiller. And the next couple of years don’t look much brighter for the big pharmaceutical companies, with numerous drug patents due to expire, potentially costing the industry billions of dollars in revenue.

“The Mercks and Pfizers are no longer unlimited growth machines,” said John McCamant, editor of the Medical Technology Stock Letter in Berkeley, Calif. “Interestingly enough, it looks like Amgen and Genentech are. We’ve had a changing of the guard.”

The century-old drug industry has historically used chemical techniques to discover its products, whereas the 30-year-old biotechnology industry has used genetic techniques. The latter approach is paying off for the leading companies, with a string of spectacular drugs for cancer and other tough diseases coming to market recently. And the companies have managed to sell them at extraordinary prices, sometimes exceeding $50,000 a year for each patient.

The split between big companies, with their rising stock prices, and smaller fry, with nearly flat prices, was reflected not only on the national scene but also in the Washington region.

MedImmune Inc., of Gaithersburg, Md., with an important preventive drug for respiratory disease in babies, was up 29 percent for the year, closing Thursday at $35.04. By contrast, Human Genome Sciences Inc., a Rockville, Md., company that gets plenty of publicity but has yet to put a drug on the market, was down 31 percent for the year, closing Thursday at $8.32.

Genentech, of South San Francisco, Calif., was the first biotech company, founded in 1976. It struggled for years, but recently has been on a roll. Genentech now sells the world’s top-selling cancer drug, Rituxan, and a recently-approved Genentech cancer product, Avastin, looks set to surpass it.

Genentech revenues are approaching $7 billion a year. An old-line pharmaceutical company, Pfizer Inc., takes in more than that from Lipitor, the world’s best-selling medicine. But Genentech is growing faster, and long-term growth potential seems to be what health care investors are looking for.

“Genentech had an incredible year as the company nailed one positive clinical trial after another in what is the best string of positive trial news we have ever seen in the biotech industry,” McCamant wrote in a recent edition of his newsletter.

The company’s stock is riding so high, in fact, that some investment professionals are worried. Morningstar Inc., the independent research firm, pegs “fair value” for Genentech shares at $70, compared with Thursday’s close of $92.06, and Morningstar rates the stock as a sell at current prices. “Genentech has had a long and impressive streak of good fortune, but drug development is probability-based, and odds are that the company will witness a setback at some point,” Morningstar analyst Jill Kiersky wrote recently.

Some analysts have a similar concern about the broad market in biotech shares. Merrill Lynch, Pierce, Fenner & Smith Inc. warned investors in a recent report that with many new cancer drugs coming to market, competition is stiffening. “The increasing availability of new cancer drugs to treat a variety of cancers is great for patients, but the market is becoming more crowded and it is becoming more difficult” to design convincing studies that can supplant previous treatment regimens, the brokerage house said.

McCamant has been urging his readers to focus their investments on smaller, undiscovered biotech companies with potentially valuable products under development. He figures that small companies will have more room to run in 2006. “You’re looking at an industry that can’t be judged with a rearview mirror, because it’s moving forward so fast,” he said.

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Affy Shares Climb 7.8 Percent on S&P 400 Listing
By a GenomeWeb staff reporter

NEW YORK, Dec. 28 (GenomeWeb News) - Shares in Affymetrix were up 7.8 percent, or $3.41, at $47.12 in mid-afternoon trading today after Standard & Poor's said it will add the company to its S&P 400 Index.

ABI Licenses Affy Microarray Patents for Gene Expression Analysis

By a GenomeWeb staff reporter

NEW YORK, Dec. 22 (GenomeWeb News) - Applied Biosystems has licensed "a number" of Affymetrix patents "related to the manufacture, sale, and use of microarrays for gene expression analysis," the companies said today.

Applera, the parent company of Applied Biosystems, has taken a non-exclusive, worldwide license to the patents.

ABI said that it will use the licenses to expand its Expression Array system and to enable customers "to use that system for gene expression, research and development purposes."

The companies did not disclose further details of the licensing agreement.

ABI's Decision to License Affy's Array IP Tops Most-Read GenomeWeb News Stories Last Week

By a GenomeWeb News editor

NEW YORK, Dec. 27 (GenomeWeb News) - What are GenomeWeb News subscribers reading? Below are the five most-read articles for the five-day period ended Friday, Dec. 23.

ABI, Continuing Pledge to Grow Consumables, Plans to Acquire Ambion’s RNA Business for $273M in Cash

By a GenomeWeb News staff reporter

NEW YORK, Dec. 27 (GenomeWeb News) - Applied Biosystems plans to acquire Ambion's research products division for around $273 million in cash, the companies said today.

With the acquisition, ABI gains entry into the consumables market for sample prep, RNAi, microRNA, and gene expression and array products.

"This acquisition is an important component of Applied Biosystems' strategy to drive growth by expanding our consumables product offering," Cathy Burzik, president of ABI, said in a statement today.

The deal, which is subject to regulatory and other condition, is expected to close in the first quarter of 2006.

The business ABI hopes to acquire develops and supplies consumables for stabilizing, synthesizing, handling, isolating, storing, detecting, and quantifying RNA. New products include microRNA and siRNA reagents used to study mechanisms of gene expression.

The market in which this business plays is believed to be around $500 million market and grows more than 10 percent annually, according to ABI. Independent figures could not immediately be obtained.

Ambion's diagnostics and service businesses will become a separate standalone company, Ambion said.

According to ABI, Ambion stands to generate more than $52 million in revenue in 2005, which would be a 22-percent improvement over last year's receipts.

Founded in 1989, Ambion's research division has approximately 300 employees. Ambion's research and development, manufacturing, and other operations will continue to be based in Austin, Texas, and report to ABI's molecular biology division.

[Business analysis on PostGenetics is available by appointment - A. Pellionisz, 30th of December, 2005]

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Perlegen, Pfizer Pen Four-Year PGx Partnership; Deal Covers IP Rights, Research Payments

By a GenomeWeb News staff reporter

NEW YORK, Dec. 28 (GenomeWeb News) - Perlegen Sciences and Pfizer have penned a four-year alliance to study whole genomes in an attempt to identity genes linked to undisclosed diseases and drug response, the companies said today.

The announcement, which comes one day after Perlegen disclosed Pfizer bought a 12-percent stake in it for $50 million, calls for researchers from both companies to conduct whole genome studies involving DNA samples from clinical trials. Perlegen will genotype the samples using Affy arrays.

Additional terms of the agreement between Perlegen and Pfizer call for the firms to share "certain" intellectual property rights that could result from the collaboration. Pfizer will provide research payments to Perlegen.

["Whole genomes" is a code-word to include "junk" DNA. In this seemingly "small news" (amounting to half the market cap of GTG) there are several "tell-tale signs". First, it is most unusual to "rush" such a deal in the last days of the year. Second, and more important, if Applera set its eyes on M/A with GTG (even to the limited extent of 25% that GTG Jacobson publicly announced) - Applera is not "the only game in town, anymore". It has become evident that the formerly "controversal, academic" issue of "junkDNA" is now a linchpin in the entirely new business model, replacing the dead "One Gene - One Disease - One Billlion Dollar Pill" paradigm by the "PostGenetics - PostGene Diseases - PostGenetic Medicine" paradigm of the 21st Century. Thus (leapfrogging expectations that "Junk" DNA will be picked up by "Big Information Technology" - although given Bill Gates' comment of yesterday it is not excluded at all), the "Gold Rush" may happen (or have happened already) by "Big Pharma" rushing to "cut their fundamental deals". Since "Big Pharma" was slowed on their track by the old business model becoming obsolete at least since 2003 and "PostGenetic Medicine" carries a price tag as big or even bigger than "Information Technology" (in which both Apple and Microsoft are sort of becoming "entertainment companies" with iPod/Pixar and X-box). With a looming "bidding war" by Applera/Pfizer (with Merck not far behind...) and possibly "Big IT" cutting in (since neither Genome of Big Pharma companies are geared to develop "the Microsoft of PostGenetics"), no wonder that GTG ("GENE" in NYSE) oscillates widely, with ten times of the volume of 3-month average trading. While for shortness of time and Holiday Season it is unlikely that GTG is already pondering over written offers in a "bidding war", the jittery Wall Street may know something that most people don't. - Business analysis is available by appointment. - Comment by A. Pellionisz, 29th of December, 2005]

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Pfizer Buys $50M Stake in Perlegen; 12-Percent Ownership Could Grow If IPO Launched

By a GenomeWeb staff reporter

NEW YORK, Dec. 27 (GenomeWeb News) - Pharmaceutical giant Pfizer invested $50 million in Perlegen Sciences, the private biotechnology company disclosed today.

The equity investment, in the form of preferred stock, gives Pfizer 12-percent ownership in the company.

If Perlegen executes an initial public offering in 2006, Pfizer has agreed to purchase up to an additional $25 million worth of stock in the company, Perlegen said.

The investment follows their first research collaboration, begun in December 2002, when Pfizer used Perlegen's DNA sample preparation, high-resolution SNP genotyping, and data-analysis capabilities.

Affymetrix, Maverick Capital, CSK Ventures, and Eli Lilly have stakes in Perlegen.

[The new paradigm of "PostGenetics - PostGene Diseases - PostGenetic Medicine" (replacing the "One Gene - One Disease - One Billion dollar pill" old paradigm) is working. Perlegen was the first significant US Genome company that took out a "non-coding DNA" licence from GTG (they were #4 from the now 24). Pfizer and Eli Lilly are obviously positioning for "PostGenetic Medicine" by buying deeper and deeper into Perlegen. No wonder that the GTG ("GENE" on NYSE) jumped on the news by 4.29% today in Wall Street. This is just the beginning - keep watching... - Comment by A. Pellionisz on 28th of December, 2005]

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Role Of MicroRNA Identified In Thyroid Cancer

The presence of only five tiny strands of RNA is enough to clearly distinguish cancerous thyroid tissue from otherwise normal tissue, scientists say.

The findings provide more evidence that an emerging set of RNA genes called microRNA (miRNA) is a powerful regulatory force in the development of cancer and other diseases. The study is published online in the Dec. 19 Proceedings of the National Academy of Sciences.

Scientists already know that some people inherit a predisposition to developing papillary thyroid cancer (PTC), the most common form of thyroid cancer, representing about 80 percent of all cases. Although changes in key cell-signaling systems and gene translocations are sometimes present in thyroid tumors, no specific gene mutations have yet been identified that are directly linked to the predisposition of this type of cancer.

That led researchers in The Ohio State University Comprehensive Cancer Center to conclude that while genetic mutations may indeed cause some people to be more likely to develop PTC than others, the mutations may not occur often enough to be readily detectable. They hypothesized that any predisposition to PTC might be more reasonably linked to a more subtle, complex interaction among several genes – suggesting a possible role for miRNAs.

MiRNAs are smidgens of genetic material no longer than 22 or so nucleotides in length. A gene, in comparison, can be tens of thousands of nucleotides long. Scientists used to think miRNAs were parts of long stretches of functionless, “junk” DNA in the genome. But Dr. Huiling He, a research scientist in the Human Cancer Genetics Program at Ohio State and the lead author of the study, says researchers are now beginning to understand how important they may be.

“The identification of miRNA ‘signatures’ in cancer and other diseases has really changed the way we think about the process of malignant growth,” says He.

Old dogma held that a gene carries a recipe for a molecule of messenger RNA which, in turn, carries a blueprint for the creation of a particular protein. Any mutation in the gene could affect the production of the protein. But recent studies have shown that protein production can also be manipulated indirectly through miRNAs.

“MiRNAs can latch on to part of the messenger RNA and scramble its ability to properly carry out its original coding instructions,” says He.

Under the direction of Dr. Albert de la Chapelle, a professor in the department of molecular virology, immunology and medical genetics at Ohio State, He and other researchers examined samples of malignant tissue from 15 patients diagnosed with PTC and compared them with normal appearing tissue adjacent to the tumors.

They found 23 miRNAs that were significantly altered in the cancerous tissue when compared with the normal samples, with three of the miRs – miR-146, miR-221 and miR-222 – dramatically overexpressed, or “turned on,” registering 11-to-19-fold higher levels of expression in the tumors than in the unaffected tissue nearby.

Further investigation revealed that two additional miRs – miR-21 and miR-181a – when coupled with the three that showed dramatic overexpression, formed a “signature” that clearly predicted the presence of malignant tissue.

“We also discovered miR-221 expression in all of the apparently normal tissue of the patients with PTC, but it was significantly overexpressed in a subset of three of the samples, suggesting that increased activity of miR-221 may be one of the earliest signs of carcinogenesis,” says de la Chapelle.

Some scientists believe miRNAs act like oncogenes, molecules that promote cell growth, and they also feel they may be tumor and tissue specific. For example, in many other forms of cancer, miRNA activity is suppressed, but in PTC, researchers found just the opposite: 17 of the 23 miRNAs they discovered were overexpressed.

According to the American Cancer Society, the incidence of thyroid cancer has been increasing slightly over the past several years. It estimates that about 25,000 new cases will be diagnosed in the United States this year.

“This is just the beginning of our work identifying the role of miRNAs in thyroid cancer,” says He. “But we are encouraged by these findings. We feel that they help point the way toward new options in diagnosis and treatment for this disease.”

A grant from the National Institutes of Health supported the research team, which included Drs. Krystian Jazdzewski, Wei Li, Stefano Volinia, George Calin, Carlo Croce and Chang-gong Liu, all of the Ohio State Human Cancer Genetics Program; Dr. Saul Suster, from OSU’s department of pathology; Dr. Richard Kloos from OSU’s departments of internal medicine and radiology; Rebecca Nagy, a genetic counselor in the Human Cancer Genetics Program; Sandra Liyanarachchi, a biostatistician in the Ohio State Human Cancer Genetics Program; and Dr. Kaarle Franssila, from the department of pathology at Helsinki University Central Hospital, Finland.

[2005 the year in which the "One Gene - One Disease - One Billion dollar pill" dogma was replaced by the "PostGenes - PostGene Diseases - PostGenetic Medicine" paradigm - comment by A. Pellionisz, 24th of December, 2005]

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Cedars-Sinai researchers demonstrate a new way to switch therapeutic genes 'on' and 'off'

Novel signaling system may eventually help make gene therapies more effective

A gene therapy research team at Cedars-Sinai Medical Center has developed a new method of signaling therapeutic genes to turn "off" or "on," a mechanism that could enable scientists to fine-tune genetic- and stem cell-based therapies so that they are safer, more controllable and more effective.

Although other similar signaling systems have been developed, the Cedars-Sinai research is the first to give physicians the flexibility to arbitrarily turn the gene expression on or off even in the presence of an immune response to adenovirus, as would be present in most patients undergoing clinical trials. This has been a major obstacle in bringing the testing of genetic therapies to humans in a clinical setting.

As reported in a study published in the January issue of the Journal of Virology, the development of a new delivery system that can more effectively regulate therapeutic gene expression has important implications for efforts to advance gene and stem cell therapy strategies that may ultimately be used to treat life-threatening neurodegenerative diseases in the clinical setting. The study, which involved laboratory rats, focused on the area of the brain that has already been the target for research into genetic therapies for Parkinson's disease.

"Since some diseases treated with gene therapy will require constant therapeutic expression while others may have periods of remission and therefore only require treatment during 'active' disease states, a system that can more closely monitor the 'how much' and 'when' the therapeutic gene is produced is a critically important tool in the development of gene therapy treatments that could help people suffering from Parkinson's and other diseases," said Maria Castro, Ph.D., co-director of the Board of Governors' Gene Therapeutic Research Institute at Cedars-Sinai and lead author of the study.

"Until now, researchers working to develop successful gene therapy for diseases such as Parkinson's have hit roadblocks such as toxic side-effects from over-expression of the therapeutic gene, and adverse events caused by immune system reactions to the viral delivery systems currently used to deliver the therapeutic genes," said Pedro Lowenstein, M.D., Ph.D., co-director of the Institute and co-author of the study. "Now, we've engineered a genetic switch in a novel gene transfer vector that will overcome those barriers and set the stage to allow the next phase of research to occur."

Gene therapy is an experimental treatment that uses genetically engineered viruses (vectors) to transfer therapeutic genes and/or proteins into cells. As in a viral infection, the viruses work by tricking cells into accepting them as part of their own genetic machinery. To make them safe, scientists remove the viral genes that cause infection and engineer them so that they stop reproducing after they have delivered the therapeutic gene.

In this study, researchers created a genetic switch system that is turned on in the presence of the antibiotic tetracycline. Therefore, if this method is tested eventually in humans, patients would need to be given this antibiotic before they begin gene therapy treatment. The switch system also produces a protein called silencer, which completely shuts down gene expression in the "off" state, thereby preventing leakage of the therapeutic gene when it is no longer needed. According to Castro, this novel vector system is much less likely to create an undesirable immune response in the host and would still be functional in the presence of an infection to wild type adenovirus (a non-engineered virus that causes conjunctivitis and upper respiratory tract infections) as is present in a high percentage of patients undergoing clinical trails. These are the main hurdles that needed to be overcome before gene therapy can be considered a safe and efficacious clinical strategy.

According to Drs. Castro and Lowenstein, the next step in the development of this new signaling system is to activate the newly developed genetic switch to actively express compounds that are known to be effective at reversing the symptoms and rescuing the damaged neurons in Parkinson's disease patients. Researchers hope to begin a Phase 1 clinical trial in humans in the near future.

HHMI Research on Evolution in Action Highlighted in Science’s "Breakthrough of the Year"

December 23, 2005

The journal Science has announced that the scientific “Breakthrough of the Year” is evolution in action. Recent experiments by four HHMI investigators were among those mentioned by Science as having provided evidence of evolution in action during the past year.

“It's been a great year for understanding how evolution works, through both experiment and theory. No single discovery makes the case by itself; after all, the challenge of understanding evolution makes multiple demands,” stated Science editor-in-chief Donald Kennedy in an accompanying editorial.

The research on evolution and nine other research advances make up Science's list of the top 10 scientific developments in 2005, chosen for their profound implications for society and the advancement of science. The Top Ten list appears in the December 23, 2005, issue of the journal Science.

In citing recent studies on evolution, Science highlighted recently published research from HHMI investigators Sean Carroll at the University of Wisconsin, Madison, David Kingsley at Stanford University, Bruce Lahn at the University of Chicago and Christopher Walsh at Harvard Medical School.

[...]

Christopher A. Walsh

Humans evolved in the most recent few moments of evolution's grand pageant. The evolutionary lineage leading to humans split off from the lineage leading to chimpanzees some 6 to 8 million years ago. But anatomically modern humans—people who looked as we do today—appeared only about 150,000 years ago (less than one three-thousandth of the time between us and the Cambrian period).

The lineage leading to humans obviously underwent profound changes since the time of our common ancestor with chimps. HHMI investigator Christopher A. Walsh at Harvard Medical School has been studying those changes in the brain.

Walsh points out that three genetic mechanisms could have caused the human brain to diverge from the chimpanzee brain. New genes may have been added to the human genome that are not present in the chimpanzee genome. Some of the genes that the two organisms share could encode subtly different proteins. Or the regulation of genes could vary—shared genes might be more or less active in the two organisms during different periods of development and in different tissues.

"We have some evidence for the action of all three of those mechanisms, and we're sorting out which of them is likely to be most important," said Walsh. Publication of the chimp genome revealed that a number of genes in humans have been duplicated and then altered since the days of our common ancestor, and some of those genes may influence the development of human brains. Similarly, many of our genes are slightly different from the corresponding genes of the chimp, although that animal's genome reveals a striking similarity in coding sequences across the two species.

But Walsh thinks that regulatory changes eventually will prove to be the most important distinguishing factor. Small changes in the expression of a gene can have dramatic effects on an organism. Researchers also have shown that levels of gene expression have changed more over time in the human lineage than in the chimpanzee lineage. Unfortunately, said Walsh, "Our tools for studying changes in noncoding DNA are very poor."

[Interesting politics, but not very good "Science". Evolution as a winner is not news at all. ET/ID never challenged the validity of Evolution as a theory - thus evolution did not need to "win". For evolution to prevail was enough that ET/ID failed to show that they have predictive theory. "PostGenetics is here - but there are no tools" - this is the "news to use" of 2005 - comment by A. Pellionisz, 23rd of December, 2005]

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Civilisation has left its mark on our genes [correction, on human Genome]

22:00 19 December 2005
From New Scientist Print Edition
Bob Holmes

Darwin’s fingerprints can be found all over the human genome. [So why restrict the analysis before PostGenetics on "genes only"?? - AJP]. A detailed look at human DNA has shown that a significant percentage of our genes have been shaped by natural selection in the past 50,000 years, probably in response to aspects of modern human culture such as the emergence of agriculture and the shift towards living in densely populated settlements.

One way to look for genes that have recently been changed by natural selection is to study mutations called single-nucleotide polymorphisms (SNPs) – single-letter differences in the genetic code. [The problem is, that this analysis, like almost all before PostGenetics, restricts investigation to "genes only" - though it is basic knowledge that "the majority of variations are found outside of genes, in the "extra" or "junk" DNA" - AJP]. The trick is to look for pairs of SNPs that occur together more often than would be expected from the chance genetic reshuffling that inevitably happens down the generations.

Such correlations are known as linkage disequilibrium, and can occur when natural selection favours a particular variant of a gene, causing the SNPs nearby to be selected as well.

Robert Moyzis and his colleagues at the University of California, Irvine, US, searched for instances of linkage disequilibrium in a collection of 1.6 million SNPs scattered across all the human chromosomes. They then looked carefully at the instances they found to distinguish the consequences of natural selection from other phenomena, such as random inversions of chunks of DNA, which can disrupt normal genetic reshuffling.

This analysis suggested that around 1800 genes, or roughly 7% of the total in the human genome, have changed under the influence of natural selection within the past 50,000 years. [What percentage of the 98.7% of DNA [before PostGenetics, 'junk' DNA shows and shows what kinds of SNPs? - AJP]. A second analysis using a second SNP database gave similar results. That is roughly the same proportion of genes that were altered in maize when humans domesticated it from its wild ancestors.

“Domesticated” humans

Moyzis speculates that we may have similarly “domesticated” ourselves with the emergence of modern civilisation.

“One of the major things that has happened in the last 50,000 years is the development of culture,” he says. “By so radically and rapidly changing our environment through our culture, we’ve put new kinds of selection [pressures] on ourselves.” [This profound question, of course, is highly debatable. In one view it is the "domestication" that causes changes in the DNA - not only, in fact mostly *not*, in "genes". In another view it is the polymorphism - in rare forms, called mutation of DNA- caused an altered behavior, "domestication". At the general mathematical level of DNA Information Theory, the upcoming book "FractoGene ... decoding 'Junk' DNA in PostGenetics" will provide some astonishing concept - AJP]

Genes that aid protein metabolism – perhaps related to a change in diet with the dawn of agriculture – turn up unusually often in Moyzis’s list of recently selected genes. So do genes involved in resisting infections, which would be important in a species settling into more densely populated villages where diseases would spread more easily. Other selected genes include those involved in brain function, which could be important in the development of culture.

But the details of any such sweeping survey of the genome should be treated with caution, geneticists warn. . Now that Moyzis has made a start on studying how the influence of modern human culture is written in our genes, other teams can see if similar results are produced by other analytical techniques, such as comparing human and chimp genomes.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0509691102)

[Short of an encompassing analysis of the entire genome - including PostGenes (formerly 'junk') - analysis of SNPs, though it is already used for diagnostic purposes, presently is fractional, and awaits a spectacular blossoming - comment by A. Pellionisz, 22nd of December, 2005]

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