First Look at Genome Operating System Revealed at Centennial Celebration; Living Test for Mad Cow Disease First Application.

Business Editors/Health/Medical Writers

ANN ARBOR, Mich.--(BUSINESS WIRE)--May 14, 2003

The germ theory of disease--a new concept at the beginning of the 20th century--inspired Dr. Frederick Novy to establish the University of Michigan Department of Microbiology and Immunology 100 years ago. This year's Centennial Celebration honors those historic events with two days of lectures presenting insights into today's revolutions in microbiology.

Among the invited speakers at the Centennial Celebration is Department graduate Dr. Howard Urnovitz, describing "The Dynamic Genome." Dr. Urnovitz helps launch the Department's second century by presenting a new concept: that the genome contains not simply a static blueprint for life passed from parents to children, but it also contains an operating system that instructs the organism how to both use and adapt genomic elements to the constant challenges of a dynamic environment. Dr. Urnovitz demonstrates how the new concept led to a practical breakthrough that will help protect the food supply--a surrogate marker blood test for mad cow disease that can be performed on living animals--and potential public health applications for understanding the role of the genome in epidemics ranging from influenza-like pandemics to the mysteries surrounding the Gulf War syndrome, chronic fatigue syndrome, and AIDS.

Central to the concept of a dynamic genome is the discovery that blood born sub-cellular particles, referred to as "microvesicles," contain "non-blueprint" RNA. In the past it has been assumed that such microvesicles were of foreign origin and they have been referred to as viruses. While microvesicles are found in both healthy and diseased animals, their RNA contents appear to be different. Dr. Urnovitz is Co-Founder and Chief Science Officer of a private genomics company, Chronix Biomedical, which is the first to report on a diagnostic test for blood born non-viral RNA with its application for mad cow disease, also known as bovine spongiform encephalopathy (BSE).

Dr. Urnovitz will be disclosing his science plan for developing the required diagnostic products to help measure and understand the role played by the genome in disease. The plan is based on a historical review of the last 100 years of mysterious influenza-like pandemics, including the current SARS epidemic. Dr. Urnovitz rejects the theory of a coronavirus as being the cause of SARS. "First, the New England Journal of Medicine study was biased in that it studied only exposed laboratory cultures that showed cytopathic effect. Why do transmissible factors have to kill a cell to be part of the disease process? Why can't pathogenic genes dysregulate cellular functions without killing the host cell?" Next, Dr. Urnovitz presents his analysis of the so-called SARS-related coronavirus gene sequence recovered from cytopathic cultures. "Frankly, I do not see a virus. I see a unique and complete rearrangement of genomic elements. For example, when I look at what is believed to be the gene sequence coding for the spike protein of this coronavirus, I see a complicated gene rearrangement of a region of human chromosome 7. As I did in our studies of Gulf War Syndrome, when I see gene rearrangements like this, I immediately search for an associated catastrophic environmental event that could have caused such genomic rearrangement."

Dr. Urnovitz traces a correlation between nuclear and chemical weapons deployment over the last 100 years and the associated occurrence of flu-like pandemics. He postulates that when animals are exposed to nuclear or chemical weapons, entirely new regulatory gene sets are expressed and packaged into non-viral RNA regulatory microvesicles. The risk of turning an epidemic into a pandemic is increased when the exposed animals are migratory birds that frequent gene-swapping hot spots like Southeast China. Dr. Urnovitz says, "The recent sightings in eastern China and Hong Kong of rare migratory birds--white cranes, grey cranes, and swans--that spend significant time feeding in the radioactive-contaminated regions of Siberia suggest that international efforts should be focused on not only hunting for weapons of mass destruction but also on cleaning up the ones that have already been released into the environment."

Siberia's Tom and Romashka Rivers are known to be highly contaminated with not only cesium and strontium-90, which could date from nuclear tests performed in the 1950s and 1960s, but also with phosphorus-32, which has a half-life of only two weeks, indicating recent contamination. Aquatic plants in the Yenisei River have been found to be contaminated with industrial radionucleotides, and rivers near Seversk, Siberia (where two nuclear reactors still operate), are reported to contain fish contaminated with radioactivity 20 times the "safe" level. All of these sites are in the path of birds migrating to Hong Kong and Eastern China, a known "hot spot" for influenza and other viral recombination. University of Michigan Department of Microbiology and Immunology Professor Emeritus and Medical Virologist William H. Murphy says, "West Nile Virus infections are a good current example of the role played by migratory birds in the spread of viral associated diseases."

Additionally, major antigenic drift among influenza viruses (H1N1 to H2N2 to H3N2 from 1918 to 1969) can be temporally mapped to above-ground nuclear testing in the flight paths of migratory birds across Siberia to Eastern China.

From his historical review of the data, Dr. Urnovitz proposes the following list of catastrophic events and associated epidemics:

-- Chemical weapons deployment in WWI and the worldwide 1918

Spanish flu H1N1 pandemic, as well as isolated smallpox

outbreaks. These include a breakthrough smallpox epidemic in

1918-1920 in a smallpox-vaccinated Philippine population;

-- Above ground megaton nuclear weapons testing in the South

Pacific in the 1950s and the H2N2 flu pandemic;

-- 1950s and '60s widespread pesticide use (e.g., DDT) and the

childhood paralysis and chronic fatigue syndrome epidemics;

-- Chemical weapons use in Vietnam along with China's and

France's above ground nuclear weapons testing and the 1968

through the 1970s H3N2 influenza pandemics;

-- Hepatitis B vaccines contaminated with regulatory genetic

elements and the emergence of AIDS in the US in the late

1970s-early 1980s;

-- Widespread pesticide use in Africa in the 1970s to present

and AIDS;

-- and Multiple toxic exposures simultaneously with multiple

vaccine administration in 1990 and Gulf War Syndrome.

Dr. Urnovitz also highlights supporting evidence rejecting the single-gene theory of mysterious epidemics. "While the current dogma states that vaccines stop viral epidemics, the historical data do not support that claim. From smallpox to polio to HIV, all vaccine attempts have been ineffective or hazardous to the vaccinee. Therefore, Chronix Biomedical's product development plan takes a different approach from the single-gene model of viral infections and associated vaccine therapeutic efforts and the company intends to develop screening and diagnostic tests based on the detection of non-viral RNA regulatory microvesicles for both veterinary and human diseases."

The first diagnostic application of the non-viral RNA microvesicle discovery is a living blood test for mad cow disease or BSE. The BSE blood test--the first that can be performed on living animals--is under development in the laboratory of Professor Bertram Brenig, Director of the Institute of Veterinary Medicine, Georg-August University, Gottingen, Germany. Dr. Urnovitz's collaboration with Dr. Brenig's laboratory has resulted in detection of a specific RNA unique to cows at risk for developing or that have confirmed cases of BSE.

The Chronix BSE blood test is anticipated to be the first licensed test that can be performed on living animals. Chronix expects to apply for governmental approval for this test during this calendar year. Current BSE tests can only be performed post-mortem on cow brain material. The post-mortem tests look for an abnormal protein known as a prion that is associated with the disease. The BSE blood test is considered a surrogate marker test since it detects blood RNA, not prion proteins.

Dr. Urnovitz's talk in Ann Arbor presents results that show that the BSE blood test is 100% sensitive on all 6 BSE cows confirmed with a licensed prion test. The BSE blood test is 100% specific on all 46 animals from known healthy herds. The intriguing part of the study is that 3.5% of cohort animals (two animals out of 57) showed a positive response in the surrogate marker living BSE blood test. Cohorts are defined as all animals born and/or raised in the same herd as a confirmed BSE case within approximately 12 months before and after the date of birth of the BSE case. Positive cohort cases may represent animals at risk for developing BSE. The current European Union regulations require all cohort animals to be slaughtered.

Chronix Biomedical, founded in 1997, is a privately-held genomics company that is developing products that address chronic diseases for both human and veterinary markets with offices in San Jose, Calif., and Gottingen, Germany. The Company's core technology is the detection of acellular nucleic acid sequences in serum, plasma, and other biological fluids of diseased individuals or animals. The Company's mission is to focus the power of genomics on creating technologies to diagnose, monitor, manage, and treat chronic diseases.