Swine flu vaccine:
The facts behind the kerfuffle
By Roger Baker / The Rag Blog / November 5, 2009
Are the big pharmaceutical companies endangering our health with risky things like swine flu vaccine? Maybe vaccines are risky, but perhaps not in the same ways and for the reasons that a lot of people are thinking, if we are to judge by the Internet chatter.
Is there a risk?
Probably the biggest flu vaccine risk is produced by not providing the influenza vaccine soon enough, because the proper federal government incentives were not there. The big pharmaceutical companies are overcharging the government, sending production offshore, withholding information, and using slow and obsolete production technology.
They may be in effect killing people who can't get the safe and effective vaccines they need in time to prevent disease. We see this with both swine and seasonal flu vaccine shortages. After vaccination, about a two week delay is needed to develop a strong immune response.
From The New York Times:
...So far, the swine flu virus looks no more virulent than a normal seasonal flu. That is bad enough. It has killed roughly 4,000 Americans and sent roughly 40,000 to the hospital. The virus is active in 48 states, and even if it begins to taper off soon, another wave might hit us early next year. Those most at risk would be wise to get vaccinated when they can find a supply...If you shop at Whole Foods, you might think that leading a healthy natural lifestyle based on their food may be all the medicine you ever need. Stores like this seem to sell a ton of herbal remedies but not much aspirin. This profitable healthy eating culture is no doubt valid, but is not enough by itself. Here is a recent recommendation for a healthy diet from the Harvard School of Public Health
One problem with current trends is that, while an increasing part of the general population might like to eat a healthy diet, more and more average folks can't afford to eat healthy fresh fruits and vegetables to go along with the staple grains, etc. Perhaps they are exhausted by work and grab a quick burger and fries and soda. Or they are conned by TV commercials into feeding their kids cheap sugary drinks and junk food snacks full of fat and sugar. The kinds of food average people eat is increasingly a function of their economic class, and this certainly affects general public health and immunity.
I agree with a lot of the healthy food thinking, but I don't believe there is much truth in the notion that just getting lots of exercise and eating a healthy diet somehow protects against contagious disease -- and that as a result we won't get sick when exposed to the various viruses to which we have no natural or vaccine-induced immunity.
The fact is that a lot of virus immunity (and many late onset chronic health problems) are actually genetic in nature and this natural immunity has often played an important role in history. The Spanish who invaded the Americas had previously suffered enough smallpox deaths to be more resistant than the Aztec Indian civilization they conquered, largely by spreading their smallpox.
Another example of natural immunity largely protected the Black slaves in Haiti where yellow fever was endemic in the early 1800s. This mosquito-spread disease then killed many of the French troops that were sent in to put down a Haitian slave revolt. This in turn helped to convince Napoleon to abandon French American colonies like Haiti, which helped lead to the Louisiana Purchase by Jefferson of a huge piece of the current United States.
However, especially since the 1930s, we have learned how to confer virus immunity using vaccines. As antibiotics lose their effectiveness -- partly through factory farming of animals such as the swine thought to have cultivated the current swine flu, and from antibiotic overuse -- the highly targeted microbe-specific vaccines will, by default, have to play an increasingly important role in medicine. Vaccines can work quite well if used properly and in advance of illness. The swine flu vaccines are thought to be about 75% effective and side effects are rare. Effective HIV and malaria vaccines may be possible in the future.
[A personal case in point: I eat a reasonably good diet at age 66, usually take a daily multivitamin supplement, and got my seasonal flu shot. However, I still got what was probably swine flu and then got a mild secondary infection, subsequently knocked out with the help of a sulfa drug. I had already gotten a pneumococcal vaccine shot to help prevent common strains of bacterial pneumonia.]
Why we dropped the ball on flu vaccine
The following, from the Council on Foreign Relations, clearly reveals that the current vaccine shortages stem from business as usual based on a bunch of fragmented business deals.
Worldwide, drug companies are scrambling to manufacture a vaccine for H1N1, also known as swine flu, which was declared a pandemic in June 2009. David Fedson, an expert in influenza vaccines and a former consultant to the World Health Organization, says the current distribution system is outmoded, and could slow or restrict the delivery of vaccines to some developing countries. "One of the reasons they're getting it late is that thus far, the distributions of vaccines from companies to countries have been handled as a series of business deals," Fedson says...It is clear that the big international pharmaceutical corporations now have no national identity, or unifying principle other than profit. Unfortunately many conventional vaccines are labor intensive and rather unprofitable to produce. Vaccines are thus natural choices for outsourcing production, according to The New York Times.
...The current problems began years ago, experts said, when vaccine companies started abandoning the American market.A new and better vaccine technology beckons
Vaccines, which involve living viruses, are much harder to make than most drugs. Profits are lower and unused flu vaccine expires after a few months. Also, vaccines are primarily intended for children, and Americans frequently sue when a child is injured.
Little was done to lure companies back until bioterrorism fears emerged after the anthrax attacks of 2001 and the H5N1 avian flu virus, which kills about 60 percent of humans infected with it, emerged in 2003, Dr. Fauci said.
In 2004, only two companies were licensed to sell flu vaccine in the United States; now there are five, but only one, Sanofi-Pasteur, has a domestic plant. The others -- GlaxoSmithKline, Novartis, CSL Ltd. and Medimmune -- use plants in England, Germany and Australia.
The drawback of relying on foreign plants was made clear recently when the Australian government pressured CSL to keep its vaccine at home instead of fulfilling its contract for 36 million doses of swine flu vaccine for the United States.
We are still trying to produce vaccines by the old fashioned but well established way of growing the flu virus in eggs and then killing it and injecting the killed virus in the flu shots. Another way is to induce immunity with a weakened virus. The nasal vaccine has a weak live flu virus. This is similar in principle to traditional smallpox vaccination which used a weak pox virus to make one pox infection lesion on your arm, thus inducing a lifelong immunity.
But both the killed virus and the weakened virus approaches are likely obsolete in our era of sophisticated biotechnology that now allows us to make recombinant vaccines. Here is what Sen. Bob Graham has recently testified with regard to the current status of our vaccine production technology:
...The United States--unlike the European Union and China--continues to use a 60-year old production method, using chicken eggs, to make H1N1 and other important vaccines. U.S. flu vaccines are safe and effective, but manufacturing can take six months, and is vulnerable to delays. The time it takes to make the vaccine is much longer than the time it takes for a flu virus to cause a pandemic. Right now, the H1N1 vaccine is being produced as quickly as possible, but millions of people will not have the chance to be vaccinated before they are exposed to the virus. Part of the slowness is due to the fact that all six US manufacturers of flu vaccine use chicken eggs. A modern and faster method to make a safe flu vaccine uses a process called "cell culture." Cell culture does not require eggs. Vaccines for polio and the modern smallpox vaccine have been produced for decades using this technology...Here Barbara Ehrenreich weighs in along similar lines:
...There are alternative "cell culture" methods that could produce the vaccine much faster, but in complete defiance of the conventional wisdom that private enterprise is always more innovative and resourceful than government, Big Pharma did not demand that they be made available for this year's swine flu epidemic. Just for the record, those alternative methods have been developed with government funding, which is also the source of almost all our basic knowledge of viruses.This describes how the U.S. medical bureaucracy dropped the ball on the swine flu virus by not rapidly employing the recombinant vaccine technology:
So, thanks to the drug companies, optimism has been about as effective in warding off H1N1 as amulets or fairy dust. Both the government and Big Pharma were indeed overly optimistic about the latter's ability to supply the vaccine, leaving those of us who are involved in the care of small children with little to rely on but hope -- hope that the epidemic will fade out on its own, hope that our loved ones have the luck to survive it...
...For more than ten years, recombinant flu vaccine has been recognized as a promising means of protection, particularly at the start of a pandemic when a novel strain of influenza appears.1 This method of producing vaccine is fast, and it can be expanded quickly from laboratory to pilot plant to large-scale production in multiple locations. Research on several recombinant vaccines, including vaccines for influenza, has been well supported by the NIH, especially by the National Institute of Allergy and Infectious Diseases (NIAID). Clinical studies have confirmed the safety and effectiveness of a recombinant vaccine for seasonal influenza.This new recombinant technology leads to cheap safe vaccines that don't need any adjuvants (non-antigen immune response boosters) to help stretch our limited vaccine supplies. Why? Because what we are really doing is inserting a few genes into a bacterium or yeast. These bits of DNA program the microbe to produce a tiny bit of the structure of the targeted virus.
However, the success of this research did not lead quickly, as it should have, to specific plans for industrial scale production of recombinant vaccine in the event of a pandemic. Elsewhere we have described a series of governmental delays and omissions. These seem to reflect, at the very least, a lack of a sense of urgency within DHHS. Specifically, two years ago DHHS solicited proposals for the production of recombinant flu vaccine for use in a pandemic. The Request for Proposals was issued in October 2007 instead of several years earlier -- a significant and damaging delay -- and the process of awarding the contract resulted in further delays. A contract was finally awarded in June 2009...
Since it is far easier to grow these special immunity-conferring microbes than to grow the live virus on living tissue, we can produce vast amounts of the pure vaccine immunizing substance fast, and thus largely avoid the traditional costs of production. This new method is fast and cheap after the up front work, but it is not business as usual for the pharmaceutical industry.
The main bottleneck in the new approach is the lab work to find which parts of the virus structure best confer immunity, followed by inserting these genes into microbes, and then testing their purified product to see if it induces immunity in ferrets, or whatever. Here is a description of the general recombinant approach, thought to be applicable to most viruses and vaccines:
Recombinant DNA technology appears to be on the verge of producing safe and effective protein vaccines for animal and human diseases. The procedure is applicable to most viruses because their isolated surface proteins generally possess immunogenic activity. Strategies used for the preparation and cloning of the appropriate genes depend on the characteristics of the viral genomes: whether DNA or RNA; their size, strandedness, and segmentation; and whether messenger RNA are monocistronic or polycistronic. Cloned surface proteins of foot-and-mouth disease and hepatitis B viruses are being tested for possible use as practical vaccines.Meanwhile, biotechnology is headed toward Asia
Two doses of the cloned foot-and-mouth disease viral protein have elicited large amounts of neutralizing antibody and have protected cattle and swine against challenge exposure with the virus. Surface proteins have also been cloned for the viruses of fowl plague, influenza, vesicular stomatitis, rabies, and herpes simplex. Cloning is in progress for surface proteins of viruses causing canine parvovirus gastroenteritis, human papillomas, infectious bovine rhinotracheitis, Rift Valley fever, and paramyxovirus diseases. In addition, advances in recombinant DNA and other facilitating technologies have rekindled interest in the chemical synthesis of polypeptide vaccines for viral diseases.
The bioengineering of bacterial vaccines is also under way. Proteinaceous pili of enterotoxigenic Escherichia coli are being produced in E coli K-12 strains for use as vaccines against neonatal diarrheal diseases of livestock.
Although the biotechnology manufacturing industry was mostly invented in the USA, it is now rapidly moving to China for manufacture of the most exotic and sophisticated drugs and bio-research materials. Tomorrow expect the best vaccines to be made in China or wherever cheap highly skilled labor and the sophisticated technology can be established. Here is an amusing link to a biotech discussion site where somebody complains about bad Chinese biochemicals. The message is immediately met with a chorus of derision, probably including many Chinese posters, who point out how much of the biochemicals used for U.S. research are already being made in China.
The new genetically engineered bio-reagents are some of the most expensive substances known. If you want a bio-engineered antibody you could easily pay the equivalent of a million dollars a gram, and there may be only one source, but it might be the only source of the only drug that works. Until somebody makes a bootleg version in India, which has been ignoring the bio-patents lately.
Expect more of these exotic and costly but sometimes very effective drugs as more of the complex genomic basis for health and disease becomes better understood. A friend of mine has an eye problem which requires the injection of a special antibody to inhibit eye blood vessel growth for treatment.
The mouse version of this special antibody costs $300 per dose, but the better human antibody version costs $3000! With this kind of incentive, we can expect a lot of the biotechnology production to keep moving offshore and the U.S. biotechnology companies to become the exclusive brokers.
Increasingly, the important issue posed by these trends is whether the manufacture and distribution of these highly specific new biotechnology drugs and their development should continue to be driven by private profit for the big pharmaceutical corporations. Or should the new drugs be developed and produced more for public benefit, much like the Salk polio vaccine that eliminated the fear of polio in the USA? Much of the basic research underlying the biotechnology was publicly funded, by the NIH, etc. Who will now benefit as we move toward our new health care system?
The mercury scare
One additional issue I’d like to address is the fear, especially voiced in conversation on the internet, of potential danger from mercury content in the flu vaccines. It is true that some vaccines still have traces of mercury. When they do, they have about 25 micrograms of thimerosal per dose, but most vaccines -- like the common childhood disease vaccines -- have none. Go to this link and scroll down and you can see which vaccines still have them and in what amounts.
The fact that only some influenza vaccines have any thimerosal at all indicates that it does not have to be there, but it helps to prevent bacterial contamination -- like in multi-dose containers from which you draw fluid repeatedly. Such contamination is dangerous when compared to any threat posed by a preservative. You can't heat vaccine to sterilize it because that would denature the antigen which is the active ingredient.
Now let’s compare this with the amounts of mercury in servings of fish. Lobster, to choose one example of a food folks often consider a treat, has about .3 parts per million as we see from this link.
Thus if you eat three ounces, or about 100 grams, of lobster, you are getting about 30 micrograms of methyl mercury, said to be a form of mercury more toxic than the ethyl mercury thimerosal in vaccine. So you would get more mercury in a more dangerous form from lobster, as well as other commonly eaten fish. Coal plants also emit lots of mercury into the environment which can end up in fish.
[Roger Baker is an Austin community activist and writer -- and regular contributor to The Rag Blog -- whose scientist parents helped to cultivate his lifelong interest in science. His work has been published in Scientific American, The Microscope, The Review of Scientific Instruments, and The History of Photography Journal. He wrote a science column called "Science Hacker" for the Society for Amateur Scientists Journal. He still likes to build scientific instruments and is currently working on perfecting an instrument useful for the early detection of insect infestation in stored wheat.]
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