The Cutter Incident

Book review: Cutter Incident by Paul Offit MD

I belong to a Rotary Club in Lacey Washington. That is weird given my experience with Rotary in High School. 1969-70 for a Senior was all about an existential solo place in a universe of like-minded people. Cooperative ventures like the Eagle/Boy Scouts or Rotary were for me, dismissed quickly. As an ASB officer, I was obliged to participate in three weekly Rotary meetings. What I witnessed there found me prejudiced against Rotary for decades. Business men at lunchtime acting like Frat Boys. I will say no more about that experience.

40 years later, a developing friendship with someone who was both a scout master and a Rotarian found me the recipient of an elevator speech on Rotary. The content is now in my elevator speech: NGO, secular, works despite governments, fields international supports to places that need it, was outlawed by the Nazis; for all these reasons, what’s not to like?

I love my Gateway Rotary, Lacey, Washington even though we meet at 7:00 AM.

I was asked to speak as the only medical professional in the club and my first talk was about vaccine technology of which I am a very strong supporter. Now, with Covid and an unprecedented vaccine process moving forward, I reviewed a book about a little known incident involving the Polio epidemic of my very early childhood. This incident has influenced anti-vaccine movements as well as a more general fear of vaccines even in those who believe they offer many benefits. The book is called, The Cutter Incident.

Vaccines are without doubt ( I am using my Rotary voice, now), the best leveraged medical technology in history. More lives have been saved and more lives have been positively changed with this technology than any other. Diseases that modern doctors freak out about because they never have seen them that were common in my youth include:

Measles: infected 4 million and killed 3,000 a year

Diptheria: 15,000 dead a year, mostly people in their teens

Rubella: 20,000 babies born with neurological defects (blindness and mentally deficiencies).

Pertussis (Whooping Cough), 8,000 dead a year.

Polio in the 50’s would kill1,000 and paralyze permanently 15,000 each year.

Uncounted are the pediatric patients who suffered from H. Influenza and pneumoccocal infections, deadly causes of skin, lung, and brain infections; all diseases that I saw in residency and which are hardly seen in the US anymore because of the vaccines delivered routinely in the first year of life.

And then there is Smallpox: Thought to have killed 500,000 people in all of world history—with meticulous use of vaccinations, Smallpox was eliminated from the natural world in the 1970’s. The smallpox scar is a mark of age/distinction when examining a patient’s skin. Of interest, in 2005, a few years after the Twin Towers, Bioterrorism was a Public Health issue and some limited vaccinations for smallpox were done in Thurston County—nurses had to be taught from scratch how to administer this unusual vaccine. We come from a time when this was truly a “thing.” If you like history, google Ben Franklin’s sad story about whether to vaccinate or not vaccinate his small son for Smallpox.

The anti-vaccination movement has been around since mandatory smallpox vaccination campaigns at the turn of the last century. There are many rational and irrational reasons to not want a vaccine. Kernie, RN, got her first influenza vaccine when she was 56 years old. Why? Amber extorted her: no vaccination, no babysitting the first grandchild. Amber is a chip off the old block.

The anti vaccination movement and the effect of a lawsuit in the setting of the polio epidemic led to a rethinking on the part of companies that make vaccines. The ability to make money is poor, and the ability to lose money as well as reputation is high in the emotional climate of our culture. Fewer and fewer companies make vaccines and in the last decades, there have been periodic shortages that were quite serious. The ripples continue to this day and the choice point of using a vaccine that has been developed and marketed at an unprecedented rate. The story of the polio vaccine is however a very different one from the various Covid vaccines.

My grandparents grew up with stories of epidemics, epidemics for which social isolation was the only reliable protection. The 1918 Flu epidemic killed 675,000 people in the United States in less than two years. It remains a higher casualty rate than all of our war dead combined.

In 1916, New York City had and unusual epidemic of polio. In the last three weeks of August, 3,500 children were paralyzed and 900 more died. The risk of dying in this epidemic if you got symptomatic disease was 25%. What made polio such a source of fear was not just the risk of death (if you got influenza, the attitude of the time was, you soldiered on), it was that from childhood, a lifetime of paralysis was yours.

Famously, in the 1920’s Franklin D. Roosevelt became a paraplegic from polio. His face graces our ten cent coins because of an effort he helped organize through Basil O’Conner who on the scale of things, was more important for the development of a preventative cure for polio than was Jonas Salk or Albert Sabin. Mr. O’Conner managed the process of research and funding for the cure for polio.

What makes the Salk vaccine different than the Covid vaccine is the technology from the 1930’s used to “inactivate” live virus. One grew the live virus in monkey cells (in glass bottles) and subsequently bathed the extracted virus in the chemical formaldehyde. Empiric research helped flesh out what concentration of formaldehyde and for how long the virus needed to be incubated but the end result was “dead” virus, incapable of reproducing and which could then be mixed in a solution that would in turn be injected into arms. Booster vaccines were needed to raise polio antibody levels to those comparable to natural infections. The process for measuring the antibodies was cumbersome—there were no direct tests for measuring the actual molecules—and it took weeks and the observation of live cells or monkeys to determine those levels.

Salk’s technique was put to test and he proved through field trials that the vaccine offered protection; there were cases of children acquiring polio in the setting of the vaccine administration. As with Covid, the explanation for this was that the vaccine does not provide immediate protection which takes weeks to months, and that exposure to disease could cause disease within weeks of vaccination.

Salk’s published “technique” was not strong on specifics. He at one point was quoted as saying something like, “a cook perfecting a recipe.” The basics were there, but the lack of specificity would in fact lead to a failure in the manufacturing process. The recipe for making a thousand vaccinations, and being sure there was no surviving “live” virus in those vaccines turned out to be different than the one needed to make hundreds of thousands of vaccines. This was controversial in the buildup to a national campaign to vaccinate and there were detractors from drug companies looking at his process not really believing he had a workable process for mass produced vaccines.

Dr. Sabin, famous for his polio vaccine (oral, sugar cube vaccination) was a critic from day one.

The regulatory process set up by the Federal Government was under resourced. In fact, the first HEW (Department of Health, Education, and Welfare) lead Oveta Culp Hobby was politically conservative and was reluctant for her department to manage the vaccine approval process. She would come under fire when after two years of trials, and a vaccine ready for distribution, she had no plan in place for distribution or mitigating costs for people with low incomes. She believed the States should and could manage this.

The under resourced federal regulators, working on an unprecedented new process developed rules for the competing drug companies to used to safely produce and distribute vaccine. There was pressure given the initial success by Salk, to get this out to the public ASAP. There was pressure to move. There was a failure: The standard process was to sample large collections of vaccine (lots) and inject the sample in monkeys. The non development over a week of polio suggested the vaccine had no live virus in it. A monkey developing polio meant the Lot was not safe. Such lots were destroyed and not distributed. There was no regulation that required they report this to the government as it was not in line for distribution. The Cutter Company, (think insect repellent) had a 30% failure rate they did not report until after catastrophe hit. Other companies had failure rates, but at dramatic lower rates that were hard to demonstrate. The Salk process was imperfect and all the companies had live virus in some of their vaccines. Cutter’s failure was head and shoulders above the other companies.

Walter Winchell was a gossipy newsman of his time; he became aware that no process existed yet to guarantee safe vaccines ie zero risk of acquiring polio, and he, without naming sources, went on national radio noting that, “little white coffins” were being purchased and stored for the expected deaths of a national polio vaccination campaign. 150,000 children were withdrawn from the field trials then on going.

The vaccine clearly worked. Virtually all polio acquired in the studies occurred in those who had received a placebo. But was the vaccine safe? All five companies manufacturing the vaccines had on and off again failures (presence of live virus) with random samplings of vaccine. Despite this, and under great pressure to not hold up the much needed relief from polio, the companies were licensed to dispense.

Cutter dispensed its vaccine in the Western US. It became clear within months that they had live virus in the vaccine. After hundreds of thousands of vaccinations, 40,000 children acquired polio after the vaccination with 200 rendered paralyzed and 10 died. This was a parent’s, and the vaccination program’s worse nightmare.

Even before the failure was understood, Cutter asked for help. No obvious flaw in their process could be found and “tweaks” were recommended. They were allowed to continue production and dispensing. The scrutiny received with the numbers above led to a much more refined review and a number of important difference between the companies came to light and a more refined process allowed for improved performance. The damage having been done, slowed the public’s acceptance for a year.

There were Federal investigations; as usual, there was a cast of villains represented in the public investigations and the press:

1) The National Foundation funded and made the basic research possible; furthermore, they had demonstrated that the vaccine worked; it did not regulate the production and distribution of licensed vaccines. They were absolved.

2) California Congressman Richard Nixon was said to have pressured the Department of HEW to license Cutter (Berkeley California), the smallest of the companies attempting to get licensed. There was no evidence for this.

3) The federal regulators, the managers of laboratory and of biological controls—all in the chain of command to the very top were fired or moved to different jobs. That is where the accountability landed.

4) Peers of Jonas Salk, many of them Nobel laureates, thought his theories on inactivating virus flawed and voted to rescind the vaccine; he was suicidal at one point. His theory was flawed but using it between 1956 and 1961, with further refinements and quality controls, no infection from vaccine was documented. With serial epidemics it became clear that if you took the three shots, you had zero risk in an epidemic.

5) Dr. Sabin never believed that formaldehyde inactivated virus was safe. His process was also confounding. His vaccine predominated for decades but then was taken off the market in Western Countries.

The polio vaccine administered by sugar cube was the invention of Dr. Sabin. Dr. Sabin’s approach was to grow polio serially for “generations” in cell culture and he found that the products of this were not virulent ie did not cause disease. The oral vaccine had live virus that reproduced in a natural way and established good immunity. With time however, the mutation rates allowed the virus to regain virulence and so vaccinated people, with live polio virus growing in them, could transmit it to others who might or might not be vaccinated. The incidence of this was low and the cost and ease of vaccination seductive. By the 1990’s the risk of spreading polio with this vaccine was greater than the risk of living without vaccines, ie there was so little polio spreading naturally in the USA. The vaccine was taken off the market (but not in the third world where the risk of polio was much higher). Today our children and grandchildren get a version of the Salk vaccine.

Was Cutter Accountable? There was a trial. Cutter was unapologetic; they believed the regulations were inadequate and that Salk had a flawed process despite the fact that they went forward with a 30% failure rate and technically did not have to report that. They actually echoed the thinking of a future president initially: “We had more cases because we came out first with the most vaccines…..” but that was in fact not true and all but one other company had no such quality problems. The fact that other companies had failure to achieve 100% safe vaccine weighed on the jury. The Jury did something unprecedented; along with their verdict came a written paragraph to clarify their decision. Apparently then, as now, this is quite unusual. The jury felt that the company had done everything right according to the standards of the time, but should be liable for the injuries caused by the vaccine. This precedent—a company could make a product correctly but still be sued for damages— would change litigation in the medical world that for many remains problematic. Variations of this precedent have seen people claim unusual things: a jury awarded damages for lung cancer “caused” by past chest wall injury. People have successfully sued for damages taking medications during pregnancy for which there is no evidence of harm. Juries feeling badly for plaintiffs suffering despite no evidence for the defendants having done wrong used the precedent to award damages: and on and on.

Cutter laboratories diversified and remained a successful company and were eventually bought out by Bayer. They weathered the storm of this very difficult time. The Government reacted: if you are going to regulate, do it right and fund it properly; some would argue they have over reached in this regard. Given this story, I have to believe there is a sweet spot. The Feds eventually established a Vaccine Injury Act in 1986 which helps mitigate the risk of vaccine damage from companies (which are regulated) to an insurance specifically set up for the rare but expected harms that vaccines cause.

Despite this insurance, those who have been involved in the delivery of babies might be interested to know that a vaccine was developed to immunize adult women from Group B Strep which is implicated in perinatal infections. The vaccine has never been marketed because of the fear of litigation likely to arise from using vaccines on pregnant women…….

I am not a very good futurologist. I was born when Polio was a huge problem in my country; it no longer is a concern to most people. A preventable disease has indeed been prevented. Errors were made—- preventable errors. There are people who believe in a “deep state” ie technocrats with a belief system not in line with regular people as it regards the role and priorities of government. This approach by Cutter reminds me that there is also a deep state in the business world—where you can follow the rules and go forward with a 30% flawed product that causes great harm to what end? Profits, Saving Face, and just letting momentum carry you forward after making an investment, damn the torpedoes……..?

The technology identified in this book looks incredibly primitive by modern standards. My positivity about the Covid vaccine is in part a reflection of the different processes for manufacturing. Growing live virus in monkey cells and then chemically bathing them to inactivate them in volume and having the body react to whatever is left from that process is very very different than using modern genetic production techniques to obtain large quantities of messenger RNA for injection. The ingredients on the bottle say it all! I hear Bones, talking to Captain Kirk about the Cutter incident. “My God Jim, they are so barbaric! Why don’t they just use leaches and call it a day!”

Late Edition Rotary article post script: Africa is now (wild) polio-free! This refers to the region administered by WHO with this goal in mind and does not include most Arab countries boarding the Mediterranean (Algeria excepted) and the Horn. Nigeria was the last country to report wild polio and that was prior to August 2020. If you consider the social and economic diversity in this region, not to mention sectarian violence, this is an amazing achievement. A plug for Rotary: being an NGO (non government organization) collaborating with WHO local officials from presidents of a country to local leaders could reinforce the message and facilitate the acceptance, in the middle of civil wars, to vaccinate the population to achieve this goal that otherwise would have been impossible.