My goal for today is to report on the various presentations given at the 4th International Bird Flu conference held in Washington, DC. I presented there on March 15th. I'd also like to talk about NanoMedicine in general with some thoughts about the future of that field.

Although this message will focus on the Bird Flu conference, I want to remind everyone that, as reported, the avian flu virus is merely one of the viruses we're interested in at the present time. Others include Human Influenza Virus, Rabies, Dengue fever (50 million cases world-wide in the past 5 years), Herpes Simplex, Hepatitis C and HIV. There are others that are of interest to the US government because of their concern about bioterrorism. Drugs for those viruses will be built on demand for the government, but they have little or no commercial applications. Currently one of particular interest is the virus that causes Rift Valley Fever which has been causing outbreaks in the Rift Valley of Kenya.

Another area of particular interest to me are viruses that cause various cancers. The first to discover this fact was Dr. Francis Peyton Rous in 1910. I had an opportunity to meet him in 1960, on the 50th anniversary of his momentous discovery. For the company, this area of research could be considered a very low priority endeavor. I do have a sneaking suspicion that more and more cancers will be found to have a viral etiology. Much like peptic ulcers that were found to have H. pylori (a bacteria) as the causative agent. For an interesting look at NanoMedicine and cancer, the National Cancer Institute nanotechnology section is a wonderful resource: Nanotechnology in Cancer. The work they're funding is absolutely in parallel to what we're doing, only their work is directed at cancer cells.

Now for some interesting history about discovery and the sheer determinism necessary to fully elucidate initial observations.

In 1928, a physician-bacteriologist named Alexander Fleming, working at St. Mary's Hospital in London returned from a long vacation to find his bacterial culture plates "contaminated" by what appeared to be a fungus. Thinking his experiments were ruined, he threw the plates into a liquid antiseptic to first sterilize and then discard them. When a visitor to the lab asked for a tour, he pulled out the only non-submerged plates to complain about his ruined experiment. Upon closer examination, he found a clear zone around the dead bacterial colonies. Then he had a "Eureka" moment that led him on a 12 year quest to determine the nature of the toxin from the fungus and the means of isolating it it.

I mention this only because Dr. Diwan, the inventor of our technology spent the same amount of time before he felt that the technology of building the nanomicelle and attaching the ligand and encapsulated drugs was ready for "prime time." He supported himself by writing software and receiving grants. Another bit of historical information is the contribution of Nobel Prize winner and the inventor of Quantum Electrodynamics, Richard Feynman. He gave a lecture at Cal Tech in December 1959 entitled "There's plenty of room at the bottom" which essentially defined the field of nanotechnology. It took many years for the tools to be developed to exploit his theoretical musings. In chemistry, the field of nanotechnology was advanced by Dr. Richard Smalley, Nobelist at Rice University where Dr. Diwan received his PhD.

Back to the conference: This time, there was great emphasis on preparedness and many of the presenters discussed various measures that were being put in place to have the ability to track all suspected cases. Some described simulations that were done in various countries regarding the response to the first human cases. Others spoke about "surge capacity"; which is the ability of hospitals and emergency rooms in the US to handle a large patient influx. Now there's a joke! I invite anyone to go to a large urban hospital on a Saturday night and tell me if there is any capacity remaining. In Los Angeles, many of the large hospitals stop accepting patients early on Saturday night. So much for "surge capacity" which lies at the core of the emergency response! Look at Toronto in 2003 and tell me if there was any extra capacity. Especially with 45% of those infected being health care workers. Seventy-five thousand deaths are projected in the first month of a pandemic in Los Angeles. Total chaos and anarchy will result. It's like the battle simulations done by the Army. Everything works so well. Fire the first shot and it all goes to hell!

In Toronto nothing worked against the virus. Ribivarin, which is a component of a Hepatitis C treatment, was given out of desperation and later was thought to have made the patients worse.

There was a general consensus on when avian flu would become pandemic in nature. It was thought to be 2 to 3 years out. Either the virus has to further mutate on its own or it has to swap genes with a highly communicable version of the human flu virus. Remember that every bird infected with the low pathogenicity strain of the virus is in itself a living laboratory and the virus is busy mutating. I was asked that question and related my own experience over the years with different influenza outbreaks. My father who was born in 1903 and died in 2000 told me what happened in 1918. He remembered clearly the chaos in New York City associated with the outbreak. During my training, I also had an opportunity to speak with a physician at Bellevue Hospital in New York City who was a young intern in 1918. What he described to me was no different than what was reported by the Vietnamese, Indonesians and Turkish doctors at the conference about the level of severe disease seen in these patients and how frustrating it was to care for them. Then in 1957, my closest friend went off to camp where he got the flu during the 1957 outbreak and died in 24 hours... literally drowning in his own secretions. Then in 1968, as a young military physician, I cared for many very ill soldiers. Quite scary!!

In Indonesia, out of pure desperation (patients were seen in the hospital on the average of eight days after onset of symptoms), people were administered TamiFlu. No one seemed to feel it impacted the course of the disease. That paralleled my own clinical experience where no one seemed to garner any benefit from TamiFlu with human influenza. I must admit that prior to my trip to Vietnam last year, I did spend $160 for 20 capsules (one course of treatment for my wife and myself) that have now expired and will be tossed.

There was also a discussion about vaccines, none of which are yet approved. The Sanofi vaccine was a tremendous disappointment because less than 45% of the volunteers who received the vaccine developed an antibody response to it. And that was with a higher dose than originally anticipated! My personal feeling is that there are four factors that mitigate against widespread use of any approved vaccine. The first is that of human nature... the hesitancy to take a vaccine against a threat that is only theoretical. Secondly is the questionable effectiveness of the vaccine since the endpoint for approval is merely the presence of antibodies. Thirdly, what will be the cost? Will insurance pay for it? An article in Saturday's New York Times addresses that general question and finds that many physicians are neither stocking nor administering certain vaccines because of the failure of the insurance companies to reimburse for them! The fourth reason will be the reluctance of many to be stampeded into taking a vaccine that hasn't been extensively tested over time. This was found during the national campaign to vaccinate everyone against swine flu in 1976. What a disaster! One person died from the flu and 250 died from the effects of the vaccination. I refused to administer it though I took care of patients who had taken it. One was a pediatrician who became quadriplegic afterwards. Another was a man who was paralyzed from the waist down and another was blinded! It was purely a political play.

I spoke about the role we predicted for AviFluCide-I, when and if approved, for the immediate treatment of avian influenza infections. The people from Roche spoke about TamiFlu and its role. They acknowledged that it wouldn't be effective unless it was administered early in the course of the disease and in large doses, which might turn out to be toxic!

So where does this leave us? We are working as fast as possible to continue our AviFluCide-I testing program, first on mice, then ferrets, and depending on FDA directives, primates. We are assuming that our work will fall under the "two animal" rule. We will get that determination when we have our pre-IND meeting with the FDA.

One final thought... we may not have a problem with H5N1 at all. It may be H9N3 or any one of a number of influenza viruses that attack us in a fully activated mode, ready to spread havoc upon the human race!

For an excellent discussion about influenza viruses, look at Wikipedia influenza.

Next time, some rambles on bioterrorism and viruses.