Archive for the ‘NIH’ Category

The 1918 flu virus and its descendants: Part 2 Rediscovering the culprit

Sunday, May 13th, 2012

many other major pandemics were associated with rodents, but not the 1918 flu

I re-read my last post a day after writing it and amended the first line, since I found it misleading. It was the worst flu pandemic ever, but I knew that smallpox, the Black Plague, AIDS, malaria and perhaps even typhus each have caused nearly as many or even more deaths over a period of years. I eventually found a rather strange, non-medical website with the "7 Worst Killer Plagues in history," and confirmed my belief that no other bacteria or virus had wreaked as much havoc in brief span of time as the 1918-1919 H1N1 influenza virus.

I wanted to find out what happened to that highly pathogenic organism and, after searching the web, realized the PBS article on the "Spanish flu" was a good place to start. It mentions that the influenza virus was not identified until 1933 and that the actual genetic identity of the particular strain involved in that pandemic (as opposed to the basic type...H1N1) was not identified for many years. The influenza virus responsible for the 1918-1919 pandemic has had many descendants, none as deadly as their ancestor.

In 1950, Johan V Hultin, a graduate student starting his doctoral studies in microbiology, got a clue from a visiting professor who suggested hunting for the virus in bodies buried 32 years prior in the permafrost of the Arctic. Hultin and his faculty advisor traveled to Alaska where flu among the Inuits had been especially deadly with 50 to 100% death rates in five villages.

early days in the Far North

Gold miners, under contract with the Territorial government, had served as grave diggers in 1918-1919 and tissue samples were recovered from four bodies exhumed in 1951. Pathology slides fit with viral lung damage and, in some cases, secondary bacterial pneumonia. But tissue cultures from the samples did not cause disease in ferrets and no influenza virus was recovered.

It wasn't until 1995 that science had advanced enough to for researchers to start the work necessary to identify the virus's unique features. Jeffrey Taubenberger, a molecular pathologist then working at the Armed Forces Institute of Pathology (AFIP), began a ten-plus-year-long project starting with autopsy tissues from the time of the pandemic that had been preserved in the National Tissue Repository. His project was stimulated by a paper published in the journal Science in February, 1995, in which preserved tissue samples from the famous British scientist John Dalton (often called the father of modern atomic theory) were examined. Dalton was color-blind and had donated his eyes at his death in 1844 to determine the cause of the defect; his DNA was studied 150 years later and the resultant publication gave Taubenberger the impetus to do the same with the flu virus.

Hultin read the first paper from Taubenberger's group, wrote to him and eventually went back to Alaska to exhume more flu victims. One was an obese woman whose lungs had the findings of acute viral infection. Samples of these permafrost-preserved tissue had RNA incredibly similar to those obtained from the AFIP National Tissue repository.

And so began an amazing chapter in the history of virology.

An Herbal Medicine that may help colon cancer patents

Wednesday, April 4th, 2012

Can herbal mixtures augment the effects of traditional therapy?

I've been skeptical about many of the claims made for herbal medicines, as they're often based on case reports or other empirical data and seldom seen to meet the rigorous standards I'm used to for new medical findings. Yet millions of people over the last four thousand years have used Oriental medicine mixtures and some of those are now being subjected to intense study.

The NIH's National Center for Complementary and Alternative Medicine has a website that provides useful links into this complex and sometimes baffling field. A 2007 survey showed 38% of Americans use CAM, often in the form of dietary supplements, where well-designed clinical trials may be lacking and the safety and effectiveness of the CAM therapy is unclear.

I want to focus on one of these CAM therapies that has been examined in detail and looks exceedingly promising...thus far.

The research of Yung-Chi Cheng, the Henry Bronson Professor of Pharmacology at the Yale School of Medicine, was highlighted in The Wall Street Journal in an article titled, "Chinese Medicine Goes Under the Microscope." He was raised in Taiwan, but his PhD is from Brown University. Now he directs Yale's Therapeutics/Chemotherapy Program and has published ground-breaking work in major research journals.

Dr.Cheng has been studying a traditional Chinese medicine for 12 years. Many of China's 75,000 therapeutic concoctions may seem strange to us, consist of various combinations of 5,000 different plants and have never been tested for efficacy in a fashion we would expect. On the other hand many of our accepted medicines originally came from botanical products. Professor Cheng decided to bridge the gap, studying one particular ancient herbal drug using modern Western methods. Initially he was met with skepticism; his colleagues were concerned that he'd find a lack of consistency in the herbal preparation. Since then Yale sponsored a biotechnology company to ensure uniformity in the plants used to produce the herbal mixture known in the Orient as huang qin tang. Here, as PHY906, it is used with traditional chemotherapy to reduce side effects.

This is a mixture of four different herbs, the flowers of the Chinese skullcap plant, the fruit of the Chinese date tree, Chinese Licorice and Chinese peonies. It's a complex melange, with 62 active chemicals that apparently must be used together, a form of polypharmacy (several drugs being given at the same time). Thus far animal experiments, reported in two scientific journals, BMC Medical Genomics and Scientific Translational Medicine have been very promising ( a conclusion in the former notes it can decrease toxicity in normal cells while promoting tumor cell death) and human Phase II studies are beginning (Phase I clinical trials are small studies looking at safety, Phase II examine efficacy, does the new drug do what its supposed to; Phase III are considerably larger and compare a drug  to existing or standard treatments).

In 2003 Professor Cheng went on to establish the Consortium for Globalization of Chinese Medicine which he now chairs. Aims of the international group include using modern methods to ensure quality control of herbals and coordinating clinical trials in disparate areas of the world.

The target is colon cancer

His work was published online in the journal Nature in a 2010 article, "How an 1,800-year-old herbal mix heals the gut." In 2011 he received a $6.7M grant from the National Cancer Institute for his project titled, "Chinese Herbal Medicine as a Novel Paradigm for Cancer Chemotherapy."

I await his study results eagerly.