The Vaccine Race: The Limits of Leonard Hayflick and the WI-38 Cell Line.

I have been anxiously awaiting the release of Meredith Wadman's book, The Vaccine Race: Science, Politics, and the Human Costs of Defeating Disease, which does a deep dive into the early history of cell culture and the development of vaccines for polio, rubella, and rabies. Wadman started researching this story for a piece in Nature in 2013 (I liked it so much that it is near the top of my list of great science blog posts.) Thus, the book is a well-researched and scientifically detailed account of how many lives have been saved and improved by these scientific advances. It also describes, with unflinching honesty, the sometimes questionable practices of researchers and doctors in the time before informed consent and clinical trial review boards. Like Rebecca Skloot's The Immortal Life of Henrietta Lacks, it is an important look at the history of medical ethics. The Vaccine Race also emphasizes why we need funding for basic research and details the beginning of intellectual property law in biomedical research.


While the book focuses on the scientific development of vaccines, Leonard Hayflick is still at the center of the action. Hayflick, an early practitioner of tissue culture, was interested in developing a normal diploid human cell line. Other cell lines in use at the time were either non-human or from cancer cells. The source of his cell lines were human fetuses obtained from legal abortions. In developing the normal diploid cell lines, he observed that the cells could not grow and replicate forever, but typically replicated only 40-60 times.This result contradicted the famous experiment of Alexis Carrel, whose normal chicken heart cells were continuously cultivated in the lab for 34 years. The Carrel result was considered dogma and so Hayflick's findings were initially met with skepticism and suggestions that Hayflick must not be culturing the cells properly. After increasingly careful repetitions with the same result, he performed a co-culture experiment using young cells from a female and old cells from a male, which showed that the cells died after 40-60 replications no matter when they were added to the culture. He finally convincing the scientific community of the existence of the Hayflick limit. Carrel's result was then called into question. Many years later, Carrel's former lab technician confirmed that the method of preparing the fresh culture media was constantly adding new, young cells to the supposedly elderly cells, allowing them to appear to grow immortally.

Images of WI-38 cells from ATCC; listed as diploid human fetal lung fibroblasts.

After 38 attempts, he found success with a cell line named WI-38 (WI for Wistar Institute), which could proliferate without problem and be infected with virus and continue to replicate. Once he had a reliable cell line, Hayflick then had to convince others of its efficacy and safety for vaccine development. The cell line was eventually used to develop vaccines for adenovirus, MMR, and chickenpox. (Of course, when the source of the cells became known, there was a backlash from religious groups who thought that there was no excuse for using fetal cells.)

The other major battle that Hayflick fought was with the NIH, who had given him a contract to distribute the cells to researchers working on certain NIH grants. When he left the Wistar Institute in 1968, he took the cells with him to his new lab at Stanford. Over the next 8 years, he distributed the WI-38 cells, first at prices similar to those of commercial distributors (like ATCC) and then at increasingly high prices, charging even more for young cells at low passage numbers. In 1974, Hayflick  interviewed for a position as director of the Institute of Aging; this spurred an investigation of his management and practices of the cell line. Eventually, Hayflick resigned from Stanford and hired a young lawyer whose expertise was intellectual copyright; this lawyer later represented many of Silicon Valley's biggest players, like Apple and Facebook. Hayflick was fighting a battle with the NIH that had little precedent. Wadman uses the WI-38 case to describe the advent of intellectual property and biological patent law and how these helped spurred the success of the biotech industry. These chapters were among the most interesting. 

Leonard Hayflick proudly displays his cell line.

The book includes some pretty harrowing details of clinical trials with early vaccines that were given to patients in mental wards, babies born in public hospitals where the majority of patients were African American, inmates in prisons whose release was tied to their participation, members of the US military, and terminal cancer patients – all without informed consent. In most cases, the vaccines behaved as expected and side effects were minimal or nonexistent, but there were exceptions. These cases led Henry Beecher (an anesthesia specialist at Harvard Medical School) to publish an article in the New England Journal of Medicine entitled "Ethics and Clinical Research" which detailed the specifics of the questionable human experiments. After Beecher's article, the tide started to change.

Overall, The Vaccine Race is an excellent read, particularly for its coverage of the history of science and medical ethics. If I had one complaint it would be that it was not as detailed about the science of viruses and vaccines, but Wadman does end on a strong, scientific note as she describes the Nobel-prize winning discovery of the enzyme telomerase, which explains the mechanistic basis of the phenomenon observed by Leonard Hayflick. 

Frankenstein's Cat by Emily Anthes looks at how genetic engineering is changing the animals around us

Frankenstein's Cat: Cuddling up to Biotech's Brave New Beasts by Emily Anthes explores how biotechnology and genetic engineering are changing the animals around us. The book delves into the science behind these new creatures as well as the ethical issues and public perceptions. The result is an easy and interesting read that makes you imagine the genetically engineered animals that could be on the horizon.






GloFish were the first commercially available pets created using biotechnology. By inserting the gene that makes jellyfish glow (green fluorescent protein, or GFP) into a common pet store find (zebrafish), the inventor was able to create a fish that glowed green in certain lights. Despite seeming relatively benign, the company was required to perform extensive research on the possible environmental impacts in case of escape before GloFish were approved for sale in 2003. Interestingly, consumers had few concerns about these new creatures and were willing to pay almost 20 dollars for each fish. The company now has a variety of other colors and species available and sells special tanks to help you enjoy their fluorescent fish.

Pharming is a branch of biotechnology where researchers use farm animals to produce a range of pharmacological products. For example, goats can be engineered to produce the protein lysozyme in their milk. Lysozyme has been shown to inhibit bacterial growth; some preliminary results suggest that the lysozyme-enriched milk can improve the immune system. The scientists behind this project hope that this goat milk could help protect children from bacterial infections. Similar approaches have been used to engineer goats that have silk protein in their milk and silkworms that make collagen instead of silk. These additives are not harmful to the animals and have a range of potential applications.

The chapter on animal cloning starts with Dolly the sheep (the first cloned animal) and makes some interesting stops along the way. The story of Carbon Copy (CC), the first cloned cat (sometimes called Copy Cat), is scientifically notable because CC doesn't look much like her calico mother Rainbow. This is due to a process called X chromosome inactivation (you can learn more about this process in my recent post on Junk DNA). The gene for orange fur is on the X chromosome. CC's genome has an inactive copy of the X chromosome from her clone mother. Thus, while CC is genetically identical, she is phenotypically different. This result was interesting to scientists, but it likely gave future customers of cat cloning some pause–what's the point of paying to have your favorite cat cloned if you can't be sure you will get a cat that looks the same?

Anthes tours a wildlife preserve and research center in Louisiana where researchers aim to develop and perfect methods for cloning animals with the long-term goal of preservation of endangered species. This is certainly worthwhile goal, but the barriers, both technical and ecological, are numerous. To me, the biggest problem with saving a species through cloning is the lack of genetic diversity. Until these problems are solved, many are banking on frozen zoos, large stocks of samples from a variety of animals that are endanger of extinction. The hope is that once cloning technology improves, it may become viable to add to the existing populations.

Roboroach from Backyard Brains

The chapter on cyborg animals was truly fascinating. For example, Anthes talks about the CIA's experiments with remote-controlled cats. Project Acoustic Kitty was predictably a failure due to the fiercely independent nature of cats. There are some notable success stories with insect cyborgs. In fact, for 99 dollars, you can build your own Roboroach. The newest approaches include the use of optogenetics, where specific neurons are made to be light sensitive, allowing researchers to control animals by shining a light. These experiments have some important applications, such as the removal of land mines and the detection of survivors in earthquake rubble, but people find animal mind control to be unsettling (even if it is a roach). It is important to consider that.

The book concludes with predictions of what may be possible in the future, like creating farm animals that are resistant to disease to decrease the use of antibiotics. Frankenstein's Cat was published in 2013 and the field has made amazing progress since that time. With the advent of the new genome editing technique CRISPR, the possibilities are truly endless, which has led to concerns about the ethical and safety considerations of this technology. Earlier this week a Chinese Institute caused a stir with its announcement of the commercial availability of gene-edited micro-pigs as pets. It will be interesting to see where we draw the line on genetically modified animals.