The Vaccine Race: Science, Politics, and the Human Costs of Defeating Disease
“The Vaccine Race shines a light over the transitional period of vaccine research.”
The Vaccine Race shines a light over the transitional period of vaccine research.
Author Meredith Wadman pulls no punches. She tells the reader, “These pages are full of medical experiments we find abhorrent today. Young, healthy, prisoners are injected with hepatitis tainted blood serum; premature African American babies with experimental polio vaccine; intellectually disabled children with untried rubella vaccine. We recoil in horror.”
As ethics standards on human experimentation had yet to be written, a reader could easily imagine the pressure to take shortcuts. In 1942 50,000 U.S. servicemen came down with Hepatitis B from contaminated yellow fever vaccine, and between 100 and 150 died. In 1952 there was a polio epidemic; 58,000 were infected and 21,000 were paralyzed.
In 1954, the first polio vaccine was invented by Jonas Salk, and approved for use in 1955. Note that Salk did not patent his vaccine. He considered it his gift to humankind.
Salk’s vaccine could be improved on as it was made from dead poliovirus. There was a push to create a vaccine made from a live but weakened virus, as it was believed a live virus vaccine would provide greater immunization over a longer period of time. Those who caught the poliovirus after being vaccinated with Salk’s dead-virus vaccine were less likely to be killed but more likely to be paralyzed.
Wadman informs the reader, “Making a live vaccine means striking a delicate balance.”
At that time viruses used for study and for creating vaccines were grown in a medium that consisted of monkey cells, duck cells, horse cells, or dog cells. The risks were that the vaccine grown in a non-human culture would not work as well when injected into humans, or the culture might contain hidden viruses that could harm humans. There were also issues with the use of human cells to grow cultures. The important factor in tissue culture was that they should not have latent diseases, which is true even for tissues cultured used for researching things other than vaccines, for example cancer research.
In the mid-1950s the cause of cancer was assumed to be environmental though there was concern that viruses could also cause cancer. In 1958, the National Institutes of Health (NIH) funded research to find a marker that would identify cancer, and in 1960 a link was found between chromosomal aberration and cancer. The impact of this discovery for researchers was the need for non-contaminated culture samples to know when an infection is present—the problem was even in normal cells, latent disease-causing viruses were common.
In the 1960s virologist Bernice Eddy at the NIH was concerned about the use of monkey kidneys for cell cultures, as these cultures might contain diseases that jumped species, in this case the potential of latent disease from passing live monkey virus into vaccines used on tens of millions of schoolchildren. The common belief was that simian viruses were killed when polioviruses were killed during vaccine creation. This was later shown to be true but not 100% true.
And so, the true-life story begins.
The Vaccine Race is divided into two parts, the first focuses on the early (1950–1960s) vaccines—primarily polio, and the invention of vaccine cultures grown in human cells. The second part primarily focuses on rubella and the rubella vaccine, that concludes with chapters of subject matter odds and ends. The common tie between the two parts is one man, research scientist Leonard Hayflick.
And here we come to Leonard Hayflick’s role in The Vaccine Race.
An obvious source of clean tissue cultures would be human fetus cells, and the obvious source of human fetuses was abortions. Leonard Hayflick was the first to grow human cells taken from the lungs of an aborted fetus to provide culture for growing viruses for creating vaccines. The successful culture, known as WI-38, has been used by doctors around the world to create vaccines that have been given to more than 300 million people, half of them U.S. preschoolers.
Leonard Hayflick was born in 1928, a time when there were no vaccines to prevent scarlet fever, measles, or polio, nor were there antibiotics to counter tuberculosis, cholera, typhus, or diphtheria.
In 1927, it was discovered that viruses could only reproduce by invading living cells, else they remained inert. What was the best way to study viruses? The U.S. Army enlisted volunteers to be bitten by mosquitos to study yellow fever. Sometimes animals were enlisted as well, as for example ferrets—ferrets could catch human influenza. And sometimes viruses could be grown in lab dishes that held animal tissue culture though successes with culture grown viruses were sporadic and inconsistent.
In 1948, a virus hunting team consisting of John Enders, Thomas Weller, and Frederick Robbins improved solutions to keep viruses alive in lab dishes, and in 1954 they received the Nobel Prize in Medicine.
Hayflick received his BA in 1952 and started working for Merck Labs in Pennsylvania. For his PhD he studied mycoplasma (bacteria that lacks a cell wall), and tissue culture at the Wistar Institute also in Pennsylvania. After his postdoc in Texas at the lab of Charles Pomerat, he was hired back to the Wistar Institute to research tissue culture.
Another researcher identified in The Vaccine Race is Hilary Koprowski. Koprowski, a WWII refugee from Poland, was hired to be Wistar’s director when the institute was at low ebb. Koprowski ran the Wistar Institute for more than 30 years. He hired top scientists (including Hayflick), renovated the institute, and provided state-of-the-art labs for virology, biochemistry, and tissue culture.
Hayflick was a hardcore researcher; he used his newborn daughter’s amniotic sac to grow tissue culture.
As part of experimenting Hayflick discovered that non-cancerous cells aged; cells would reproduce only a limited number of times before death. This discovery was groundbreaking. It was believed at that time normal cells would reproduce forever. The problem for Hayflick in making this discovery was that he wasn’t famous enough to be believed.
An important step prior to mass production of a vaccine was testing them on human subjects. Koprowski tested polio vaccines on institutionalized intellectually disabled children. Other researchers tested polio vaccines on babies, including premature babies weighing as little as 1.75 lbs. In 1961 poliovirus vaccines were tested on babies born to women in jail. The incentive for the imprisoned mothers to allow testing was to be given more time with their babies.
If this wasn’t enough, one problem for Hayflick in using human fetal cells for tissue culture was in getting a human cell line accepted by federal regulators. Evidence for safety involved injecting cells into dying cancer patients, “volunteers,” to see if the injected cells turn cancerous. Hayflick acquired 17 “volunteers.”
Hayflick’s test was successful, and the demand for fetal cells soared after publication of his landmark paper that established that a human cell strain from one set of fetal lungs could be clean and safe at the beginning with no worries for the future.
The demand for fetal cells resulted in a depletion of stocks. At that time there were difficulties in acquiring fetuses for medical experimentation. In the early 1960s abortion was illegal in every state, and in certain states illegal without exception even if the woman’s life was endangered. On the other hand, at the hospital at the University of Pennsylvania associated with Wistar, legal authorities tolerated abortions. These abortions were considered “therapeutic,” and not criminal. At that time the estimated criminal to therapeutic abortion ratio was 100 to 1, with the burden falling on the poor.
In 1962, the National Cancer Institute, part of the NIH, entered into a contract with Wistar Institute (valued at $1 million in inflation-adjusted dollars) to create new human tissue culture stocks. To get started, Hayflick would need more than one fetus and the parents’ medical histories. He also needed a partner scientist. To this end he partnered with Sven Gard, a Swedish researcher who was on sabbatical at Wistar. The tissue culture that became the source of WI-38 stock came from the aborted fetus of Mrs. “X,” from Sweden, who was not informed of her donation. “Mrs. X had no idea that her fetus had ended up anywhere but in a medical waste incinerator.”
The second part of The Vaccine Race Wadman provides the backstory of doctors and technicians who worked on the rubella vaccine, along with details of how the rubella virus acts, and rubella’s long-term effects.
Rubella is also known as German measles. Its symptoms are mild, and two-thirds of those infected may not even be aware they have it. The consequence for a pregnant woman however is horrific; the infection takes a severe toll on her developing fetus.
Rubella outbreaks are cyclical. In June 1940 a rubella outbreak lead to very unlucky babies born nine months later, though it took until the 1950s for a study on the 1940s outbreak to be accepted. Statistics revealed only one in three babies would be born healthy.
After the rubella outbreak of 1962 the virus was captured in a lab dish. A test was formulated that required a throat swab and blood test. The problem with early rubella tests was it would take ten days to get swab results, which was not always accurate, and the more accurate blood test took four weeks for results, which is too long to wait for any pregnant woman. Unsurprisingly, the 1962 outbreak led to an increase in abortions.
The rubella outbreak of 1964 was the worst since the U.S. began keeping records 40 years earlier. It was estimated that 12.5 million Americans were infected. A rubella vaccine would have a large number of customers; there were 3.6 million children born annually in the 1960s, and 39 million girls and women of childbearing age in the U.S. When researchers needed cultures to test vaccines, they went to Wistar for WI-38. Because of these numbers bigger pharmaceutical companies entered the vaccine business and smaller institutes began merging or closing.
As with polio, rubella was also tested on children. For these tests Wistar experimented on children in a Catholic orphanage. The letter requesting access to children for testing from Wistar to the orphanage did not mention that the vaccine was made from and grown in tissue culture made from aborted fetuses. The test was not of a vaccine. At this time there was no vaccine. The test was to give the rubella virus to children to study how the infection spread. (Female caregivers at the orphanage were tested first to see if they were already immune, and moved out of the ward if they were not.)
Wadman points out this was not the first or second experiment in the name of science to intentionally give children diseases. It wasn’t until 1966 with the journal article “Ethics in Clinical Research” by Henry Beecher published in the New England Journal of Medicine that there was any ethical reform of testing. This article identified 22 human experiments done between 1948 and 1965 that risked health or life of their subjects, including injecting living cancer cells into “volunteers” just to see what would happen.
In 1967 an improved rubella test was developed, though by 1968 no rubella vaccine had yet been approved for manufacture. Varieties of the vaccine that were made from non-human cultures at that time had unwelcome side effects. Though the vaccine made from WI-38 was better, the NIH hesitated to approve any vaccine made from human culture. The NIH finally approved a rubella vaccine in 1978. Manufactured by Merck, it was made from WI-38, and is still used in most of the world today.
Wistar’s grants from the NIH were scheduled to end in 1967. The NIH contract stated that at the end, product produced under the grant were to be transferred to the NIH. This meant transferring the remaining stocks of WI-38 to the NIH. The transfer never occurred, instead, Hayflick left Wistar for a professorship at Stanford taking most of the remaining WI-38 with him. In 1974 Hayflick incorporated and transferred ownership of his WI-38 stock to Cell Associates. As president of Cell Associates, Hayflick began to sell WI-38 to Merck; the sales were valued at $4.8 million in 2016 dollars.
One can guess where this is heading. . . .
The NIH figured out what Hayflick did in 1975 and began an investigation that was followed by a criminal probe and lawsuit. Hayflick returned his remaining stock of WI-38 to the NIH; he also resigned from Stanford. When the news of the criminal probe hit the front page of the New York Times and Science magazine, research institutions that had been interested in using WI-38 begin to shift to alternate strains of human culture (though still based on Hayflick’s methods).
There was a five-year legal battle over the ownership of the WI-38 cells. Over the five years there is a seismic shift in the legal landscape. Laws on grants changed to allow universities to patent inventions that were funded by the government. Though what Hayflick did was against the law at the start of the lawsuit, his actions would have been legal by its end. The legal battle ended in compromise, and Hayflick’s case was settled out of court.
The original ampules that held WI-38 and the polio vaccine made from it are now in the National Museum of American History. WI-38 is still in use today and cultures grown from copycat methods have been used to make six billion vaccines over a range of viruses all over the world.
Though Hayflick’s role in the vaccine race ended in 1981, there’s more to the book. The Vaccine Race has a chapter on the science of cell aging, also known as the “Hayflick Limit.” There is a chapter on the controversy of using aborted fetuses for medical research. There are several short pieces on the update to the rabies vaccine and the invention of the chickenpox vaccine. The last chapter addresses current trends in antivirus science and ethics of medical experiments. The epilogue offers a “where are they now?” of The Vaccine Race‘s principle characters.
This reviewer sees few faults in The Vaccine Race. One is the book could have used a little tighter editing, as some passages drag. Every character, no matter how minor has a backstory and though there is a significant amount of scut work in biological research, detailing it does not advance the storyline, nor does enumerating Wistar’s building maintenance, nor does following every twist and turn in Hayflick’s legal battle.
The Vaccine Race shines a light over the transitional period of vaccine research.