Deciding Which Risks to Take

No medical treatment is risk-free. Paul Offit’s new book covers the history of innovations that went awry and advises how to balance the risks of new medical innovations with the risk of not treating.

It is always risky to use a new treatment before all the evidence is in, but it’s also risky to let a serious illness go untreated. Paul Offit’s latest book You Bet Your Life is about the “long and risky history” of medical innovations, giving readers much to consider while trying to decide which risk is greater.

Paul Offit is coinventor of a rotavirus vaccine that has been credited with saving the lives of hundreds of children every day. He is a practicing pediatrician at the Children’s Hospital of Philadelphia and a vaccine expert who has served on committees to advise the government. He has written several books on vaccines and now is branching out to address other subjects.

Medical breakthroughs are happening every day. They offer wonderful benefits, but as Offit says, “virtually every medical breakthrough has exacted a human price” and some people will surely die if they choose to wait for better evidence.

If we don’t learn from history, these tragedies will be repeated. In April 2020 the FDA granted an Emergency Use Authorization to hydroxychloroquine for the treatment of COVID-19, although “no study had ever found that it worked”. More studies showed that it didn’t work for COVID-19, that 10% of recipients suffered severe heart arrhythmias, and some of them died. The FDA had to withdraw its approval after only two months. With that in mind, many people refused to take the new coronavirus vaccines that had been developed at “Warp speed”. They thought they were avoiding risk, but their choice was not risk-free. It was a choice to risk infection, hospitalization, long-term disabilities, and death.

Offit takes us through the history of several medical innovations, including heart transplants, blood transfusions, anesthesia, biologicals, antibiotics, vaccines, x-rays, chemotherapy, and gene therapy. I thought I knew about the history of these innovations, but Offit fleshes out the story with details that were new to me.


Most of the early heart transplants failed, but the patients “weren’t gambling with their lives, because their lives were at an end”. With the transplant, they died; but without the transplant, a certain death was imminent. Any risk seemed acceptable to the recipients. I knew effective transplants had to wait for technological advances and drugs that could prevent rejection (although they increased the risk of infections), but I hadn’t realized the importance of one impediment: there were no generally accepted criteria for brain death, and surgeons harvesting donor organs from a brain-dead patient could be tried for murder. Eventually, criteria for brain death were developed that were widely accepted and even supported by the Pope. But there are thousands of patients on the waiting list for a heart transplant, and a third of them will die while waiting. Offit hopes that genetic engineering may solve this problem by altering pig hearts so they can be used in humans.

Blood transfusions

The first three blood transfusions from animals (2 lambs and a calf) to humans were done in 1667 and they seemed to work. As Offit describes the second case: a drunken, middle-aged butcher was paid to receive blood from a lamb. After the procedure, he “jumped off the table, butchered the lamb, threw it over his shoulder, and ran off to a local bar to get drunk.”

The fourth patient died, and the surgeon was tried for murder. He narrowly escaped when the patient’s wife was executed for poisoning her husband. The publicity around this incident led to transfusions being declared illegal for the next two centuries; they were even banned by the Pope. After blood typing was discovered and the problems of clotting and infection were solved, transfusions became routine. A bit of trivia: in a paternity suit, blood typing proved that Charlie Chaplin was not the father of his mistress’ child, but since it was so new, blood type evidence was not admissible in court. A jury ruled that he was the child’s father, although he couldn’t possibly have been; and he had to pay child support and legal fees. Then, in the 1980s, Ryan White, a boy with hemophilia, developed AIDS from a blood transfusion and died. All Hell broke loose. Today, blood transfusions are handled with better safety precautions and better screening, and the risk is minimal but not zero.


Remember John Snow, the doctor who identified the cause of a cholera epidemic and stopped it by removing the handle of the Broad Street pump? I was surprised to learn that he was the same doctor who gave Queen Victoria chloroform for childbirth, which convinced many other women to accept pain relief for labor. Unfortunately, chloroform proved more dangerous than ether or nitrous oxide; but it continued to be used for decades before it was replaced by safer anesthetics.

Tetanus from diphtheria antitoxin serum

The blood of a horse named Jim had been successfully used to supply many batches of the antitoxin that effectively treated diphtheria. Remember Balto, the sled dog who rushed the lifesaving antitoxin to Nome? When Jim developed tetanus, his blood could no longer be used, and the lab personnel were instructed to discard his blood samples. Human error by a janitor resulted in the tetanus-infected blood being mixed with the safe blood, and 13 children in St. Louis died unnecessarily. There were other innocent victims. People elsewhere were frightened by the disaster in St. Louis and refused treatment: the death rate in Chicago increased by 30%.

The Elixir sulfanilamide disaster

Prontosil was one of the first antibiotics used to treat humans. Gerhard Domagk was awarded a Nobel Prize for discovering its effectiveness, but Hitler refused to let him travel to Sweden to receive it. The Massengill company dissolved the active ingredient sulfanilamide in diethylene glycol to make a convenient liquid preparation for children. They didn’t test it for safety. By the time they realized diethylene glycol was a poison related to antifreeze, 105 people had died. The Food, Drug, and Cosmetics Act was passed to prevent similar disasters, but the Massengill company was never held accountable. It was only fined $26,000 for misbranding and had to pay $148,000 to settle damage claims.

Polio vaccine 

The Salk polio vaccine saved countless lives, but it also caused a man-made polio epidemic with tens of thousands of cases of paralysis, hundreds of them permanent, and 10 deaths. Offit asks, “Why don’t we know this story?” The Salk vaccine was not the first; two earlier polio vaccines were developed in 1934 and 1935. Both led to paralysis and were withdrawn. Offit explains what happened and why 20 years passed before anyone dared try again.

Salk’s vaccine worked, but one manufacturer, the Cutter company, had to recall their product after two specific lots had paralyzed 51 children and killed 5, and 74 unvaccinated family members of vaccinated children had been paralyzed. In total, 70,000 people had developed polio and ten had died. Offit explains why: Salk had made a false assumption about the straight-line virus inactivation curve, Cutter had used an inferior glass filter, safety tests were “woefully inadequate”, they let the filtered virus sit in a refrigerator for weeks before inactivating it with formaldehyde, and they never constructed a graph to prove that formaldehyde was killing the virus reproducibly and in a straight line. Offit calls this the Scale-Up Incident; it illustrates some of the things that can go wrong when new vaccines are mass-produced by different companies.

The vaccination campaign switched to the Sabin oral vaccine. It was effective and easy to administer, but it could mutate back to a virus that resembled natural poliovirus. This only occurs in one of every 2.4 million doses, but in 2000 the US switched back to the safer Salk inactivated vaccine.


X-rays were an incredibly useful aid to diagnosis, but radiologists were slow to appreciate the risks of radiation. Offit tells of a 1920 professional gathering of radiologists “where so many attendees were missing hands and fingers that when the chicken dinner was served no one could cut their meat”! As a child, I remember seeing x-ray machines in shoe stores to assist in shoe fittings; they weren’t banned until the 1970s.

Other risks

Offit goes on to cover the history of other potentially risky innovations, including chemotherapy and gene therapy. He illustrates these with fascinating stories. In 1946, a 52-year-old man developed hoarseness, eye pain, and inability to speak or swallow; the cause was a large tumor at the base of his skull. Conventional treatment with radiation was not helpful. After treatment with a new chemotherapy drug, a folic acid antagonist, “the tumor shrank and he gained back most of the eighty pounds he had lost. By 1948, he was well enough to put on his old New York. Yankees uniform – the one with the number 3 on the back – and attend the 25thanniversary of the opening of Yankee Stadium. His name was Babe Ruth.”

Risk is unavoidable

Offit stresses that no treatment is risk-free. He says:

…people should make the most informed, most clear-eyed, most dispassionate decisions using all of the information available, knowing that decisions under uncertainty might be the wrong ones. Every choice involves risk, even the simplest ones.

Offit ends the book with a chapter on living with uncertainty. If we don’t learn from the disasters of history, they are sure to be repeated. Unanticipated tragedies are unpreventable. Some people think that when someone is sick or dying, any therapy is worth a shot. But Offit reminds us that “if a medicine doesn’t work, it can only do nothing or hurt”. Animal testing can be falsely reassuring, since “mice lie and monkeys exaggerate”.

Conclusion: A very worthwhile book

Offit’s research is thorough and impeccable. He writes well, and he’s a great storyteller.

Reading this book will inform you and entertain you, and it will give you much to think about for your future decisions about innovations in medical technology. I highly recommend it.

This article was originally published in the Science-Based Medicine Blog.

Dr. Hall is a contributing editor to both Skeptic magazine and the Skeptical Inquirer. She is a weekly contributor to the Science-Based Medicine Blog and is one of its editors. She has also contributed to Quackwatch and to a number of other respected journals and publications. She is the author of Women Aren’t Supposed to Fly: The Memoirs of a Female Flight Surgeon and co-author of the textbook, Consumer Health: A Guide to Intelligent Decisions.

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