Rubella, or German measles as it is sometimes known, is a devastating diseases. Until the 1960s left thousands of children suffering from birth defects if their mothers were exposed during pregnancy, but that all changed when a young scientist, Leonard Hayflick, produced cells that could be used safely in the production of vaccines.
It was a development that would protect hundreds of millions of people worldwide in the following years, and in her book The Vaccine Race: How scientists used human cells to combat killer viruses, Meredith Wadman explores this great leap forward in medicine.
We asked her a few questions about the book, shortlisted for the Wellcome Book Prize, the ethics behind Hayflick’s work, and the future of medical research.
The book tells the story of biologist Leonard Hayflick – what did he do and why did this particular story interest you so much?
Leonard Hayflick, who turns 90 next month, was from 1958 to 1968 a young biologist in Philadelphia at the Wistar Institute, an independent research institute tucked away on the campus of the University of Pennsylvania. Hayflick grew cells from a series of foetuses he obtained from abortions performed at the Hospital of the University of Pennsylvania, just across the street from the Wistar, and he made an astute observation that turned conventional scientific wisdom on its head.
As his foetal cells in their lab bottles began to divide less vigorously after several months, and then to stop dividing altogether, and then finally to die, he realized that normal, non-cancerous cells grown in culture are as mortal as you or me. They die. And this opened a field of study that is hugely important to this day: cellular aging. The number of divisions that normal cells undergo before dying in their lab dishes is called “The Hayflick Limit.”
But Hayflick made another huge contribution, and this is what captured my imagination and led me write the book. In 1962, Hayflick obtained cells from a Swedish foetus that was legally aborted. (The woman having the abortion was never asked her permission; in the book I call her Mrs. X.) The cells he grew from Mrs. X’s foetus are called WI-38 cells, and in 1962, Hayflick froze some 800 vials of these cells, each containing 3 million or so cells. (The cells, when thawed after freezing, even after half a century, will gamely begin dividing again.)
Hayflick’s purpose with the WI-38 cells was to create clean, safe, micro-factories for making human viral vaccines. At the time, the most important vaccine of the day, polio, was made in monkey kidney cells, which often had hidden monkey viruses lurking in them – potentially dangerous viruses. Eventually, with Hayflick’s avid efforts and campaigning – and despite roadblocks thrown up by obdurate regulators – the WI-38 cells were widely adopted for vaccine making.
Most importantly, they are used to make vaccine against the foetus-damaging rubella virus. In the early 1960s, rubella, also known as German measles, led to the births of tens of thousands of damaged infants, and untold numbers of stillbirths and abortions. Thanks to the vaccine, it has now been wiped out in the Western Hemisphere.
Where do you think his scientific discovery ranks among the breakthroughs in modern medicine?
Hayflick’s discovery, which I should note was achieved in partnership with his Wistar colleague, the chromosome expert Paul Moorhead, was ground breaking. It was a descriptive discovery. It said: “This is what we have observed to happen to normal cells grown in the lab.” It did not say why this happened. The greatest discoveries answer the “why” question. And so, it was Elizabeth Blackburn, Carol Greider and Jack Szostak who in 2009 shared the Nobel Prize in Physiology or Medicine for providing the “why” behind Hayflick’s discovery.
They discovered how chromosomes are protected by telomeres, the shoelace-cap like structures on their ends, and they discovered an enzyme called telomerase that plays a key role in that process. It turns out that with each cell division, the telomeres are clipped a little shorter, and when they are clipped down to a stub, the cell stops dividing. Their discoveries were hugely important both for understanding aging and for understanding what goes wrong in cancer.
Do you think Mrs. X really had no idea about what happened to her aborted foetus? Was she only angry about it and not happy that it went on to helping so many people?
I don’t just think, I know that Mrs. X had no idea what happened to her foetus until several months after the abortion. Hayflick, having derived the cells, and frozen 800 vials of them, knew that he would need a clean bill of health from Mrs. X. He would need this in order to persuade companies and regulators that the cells could safely be used for vaccine making.
They would want documented assurances that Mrs. X was not suffering from infectious disease at the time of the abortion and had no family history of cancer. (The main fear of regulators was that the WI-38 cells somehow harboured a cancer-causing virus that would be transmitted and cause cancer in vaccinated people.)
So Hayflick asked Sven Gard, the top virologist at the Karolinska Institute, who had arranged for the dissection of Mrs. X’s foetus, and the shipping of its lungs to Hayflick in Philadelphia, to obtain Mrs. X’s health records. Gard in turn delegated this delicate task to his young lieutenant, a physician and researcher named Margareta Böttiger. It was when Böttiger approached Mrs. X’s family doctor, and the doctor’s nurse, that Mrs. X was rudely awakened to the fact that her foetus had been taken and used in research without her consent.
As to Mrs. X’s feelings, when my Swedish translator interviewed her in 2013, Mrs. X was angry. “They were doing this without my knowledge. That cannot be allowed today,” she said. And she wanted this chapter of her life left closed. She had absolutely no interest in what had become of the cells, even when told that they had enabled the development of vaccines that have saved millions of lives.
The whole story raises serious ethical debates within the science of medicine – do you think Hayflick did the right thing in terms of using human foetuses?
If you are asking whether Hayflick did the right thing in terms of using human foetuses without the mother’s consents, Hayflick was a man of his time and needs to be viewed in that context. Today, our standards say that it is clearly abhorrent to take a woman’s foetus and use it in research without her knowledge or consent. In those days, it was common practice.
I am not saying that this makes what he did okay, only that it makes it understandable given his social context. There were no consent rules in place of the kind we have today – not for the use of tissue, and not for experiments on human beings either. It’s a good thing that our ethical requirements of researchers today are vastly improved from those bad old days.
If you are asking whether Hayflick did the right thing in using human foetuses because of their moral status, I would say that the answer very much depends on your views on abortion. Hayflick felt, and I think most people who support legal abortion would agree, that the abortions were going to be performed in any case, and by his use of the foetuses, possibly something good could come for science and human health. But if you are opposed to abortion, then this use of a foetus is not acceptable, just as abortion is not acceptable.
What do you think would have happened to the human population if the WI-38 sample hadn’t been created and distributed?
Vaccines would certainly have continued to be made – in fact, several vaccines were developed in the 1960s and later that did not use the WI-38 cells, or an analogous group of cells from an aborted foetus that was created in Britain in 1966, called MRC-5 cells. But in the absence of these two cells lines, possibly some vaccinees would have been unnecessarily endangered as vaccines continued to be made in animal cells.
Consider, for instance, that an outbreak of the deadly Marburg virus killed seven people and sickened 25 others in that German town in 1967. The source of the virus was a group of African green monkeys that had been imported from Uganda; their kidneys were used in vaccine-making.
In the prologue you say, “we might also remember, when judging the men who took advantage of vulnerable human beings in order to advance both human health and their own careers, that they were creatures of their time, just as we are of ours” – do you believe terrible things are happening in our world today within medicine, and general science that are just accepted or avoided?
When I wrote that sentence, I was thinking in particular of animal research. I believe that, 100 from years from now, our great-grandchildren may well ask how we could have countenanced the confinement, pain and suffering of untold hundreds of millions of intelligent, feeling, lab animals to the ends of human health and knowledge.