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Variolation, Aviation, and Genetic Modification: Progress in the Face of Fear and Danger

The views expressed are those of the author and are not necessarily those of Scientific American.

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A man with smallpox circa 1912. Click for source.

In 1721, a small pox epidemic was ripping through the colonial city of Boston.

Cotton Mather, a Reverend and Royal minister, convinced the physician Zebadiah Boylston to perform an arcane medical procedure on two slaves and Mather’s own son. The procedure, called “variolation,” involved piercing the skin of the patient with needle that was contaminated with small pox. This involved cutting the skin or causing an abrasion on the patient, then applying infectious fluid from a small-pox pustule. In other cases small-pox scabs were first dried, and then rehydrated and coated onto the inoculating instrument.

Mather wasn’t the first to try this procedure – the earliest definitive evidence of the practice is from 15th century China, though other accounts date the practice even earlier. Mather learned of the practice from an African slave, but had difficulty convincing physicians to try it. The only university-trained doctor in the city, William Douglass, refused and excoriated Mather for trying. Douglas was wary for good reason – variolation involves intentionally infecting someone with a live virus, and at the time the dose of the inoculum was difficult to control (few people were even aware of bacteria, let alone viruses, and the germ theory of disease would not even have experimental evidence until almost 100 years later). Variolation is not like a modern vaccine – patients would contract small-pox, but the hope was that it would be a mild form, and would prevent natural infection that could be deadly. However, it ran a serious risk of giving someone full-blown infectious small pox. And Small pox is a terrifying illness – it kills almost a third of those afflicted and leaves many of the survivors horribly scared.

Thankfully, Boylston was largely successful, and continued to perform the procedure beyond his initial three subjects. Other citizens of Boston were horrified. They feared that the practice could make the epidemic worse (not an unfounded fear) and kill thousands of people. Others worried (again, with justification), that the procedure could transfer other disease like syphilis. One angry man even tried to assassinate him. Another threw a bomb into the window of Cotton Mather.

Ultimately, most of Boylston’s patients survived the epidemic, while nearly 6,000 people (half the city’s population at the time) contracted the disease, and about 15% of those died. Later, Edward Jenner would use the principal behind variolation to develop the first true vaccine for small-pox, and in 1980, the disease was eradicated from the face of the Earth.


The Wright Brothers' Plane (click for source)

In 1903, a man lifted off from the ground in a heavier-than-air machine flying under its own power.

I’m no historian, but it seems as if humans have been dreaming about flight as long as there have been birds and dreams. According to the fount of all knowledge, the Chinese were making kites over 2000 years ago, and  the ancient greeks made mechanical birds. Humans have even been flying (or at least gliding) for quite a while, strapping themselves to gliders or jumping into baskets under balloons, but the real advance came in the early 20th century when Orville and Wilbur Wright (or Gustav Whitehead?) built the first powered, controllable heavier-than-air flying vehicle.

This first aeroplane was crap – it traveled less than 10 miles per hour (and likely only worked because it was flying into a 30mph headwind), and was incredibly difficult to control. Even a decade later, when European nations first started using planes in combat, they were incredibly unsafe – even skilled pilots were frequently killed in crashes. The best fliers could not compete with failing engines or even inclement weather, and the death toll was outrageous.

Of course, these days air travel is incredibly safe, and has changed the face of the globe.


A schematic for the production of recombinant DNA. (click for source)

In 1973, Herbert Boyer and Stanley Cohen artificially transferred a gene between two species of bacteria.

Later the same year, they successfully transferred a bacterial gene into a frog embryo, showing that the same gene could function in organisms from different kingdoms. In the last 35 years, our ability to manipulate life has proceeded at a staggering pace. The technology Cohen and Boyer pioneered is now commonplace in labs all over the world. In fact, later this afternoon I’m going to use enzymes from two different species of bacteria and another enzyme from a species of archaea to hook one piece of a human gene to a piece of a rat gene, then make copies using E. coli and then use a human cell line to make a virus that will integrate that my new gene combo into a type of mouse cell. It’s exhausting when you write it out like that, but this procedure is actually trivial.

Of course, others are using similar technology not in a lab to make experimental tools, but to create food crops that will end up on tables. This worries a lot people. Proponents of the technology point to current breeds of genetically engineered crops can resist fungal or insect pests, resist certain herbicides, or even increase nutrient production in staple crops. Many argue that further development of the technology will help reduce water use, or produce higher yields on smaller amounts of land. Opponents argue that using this technology in food is dangerous, might produce new allergens (see my take on that fear here), or somehow damage the environment.

And besides, say some critics, the technology isn’t event that good anyway:

Breeding continues to outpace GE and likely will continue to do so, and agroecology is much better at addressing many of these issues, especially over-reliance on scarce resources and pesticides, and resilience in the face of climate change[...]

Breeding, which continues to be more successful for all types of properties that [Mark] Lynas mentions—drought tolerance, increased yield, nutrient enhancement, pest resistance, and more—costs about a million dollars per trait. Failure of GE traits, such as virus-resistant sweet potatoes in Africa, needs to be considered more seriously as one possible explanation for the dearth of available GE traits so far.

Looking at the Wright Brothers’ plane, I wonder if any spectators remarked, “That thing only goes 10 miles per hour, clearly traveling by steam engine is superior.” I know that some policy makers in Britain after WWI (I’m reading a biography of Winston Churchill that talks about this) thought that the airplane was not worth investing in, and Churchill himself (despite being a flying enthusiast and founder of the Royal Air Force) thought that airplanes would never be able to sink a battleship and would have limited usefulness in combat.

Clearly, Dr. William Douglas thought the dangers of variolation were not worth the risk.

What will we say in 100 or 200 years about the fears associated with genetic engineering of food crops? Surely, some of the fears may be founded, others are probably spurious. I applaud anyone that’s fighting to change our agricultural system or strengthen health and safety regulation, but those efforts should be focused on outcomes, not the technology. Conventional breeding is certainly capable of producing new allergens or posing new health risks. Organic farming can be done using monoculture, with heavy pesticide use and in unsustainable ways. Let’s push to improve the sustainability of farming regardless of the technology used to do it.

Kevin Bonham About the Author: Kevin Bonham is a Curriculum Fellow in the Microbiology and Immunobiology department at Harvard Medical school. He received his PhD from Harvard, where he studied how the cells of the immune system detect the presence of infectious microbes. Find him on Google+, Reddit. Follow on Twitter @Kevbonham.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. dogctor 3:15 pm 10/23/2013

    If efforts should be focused on outcomes of this technology, the outcome today are superweedsis and clusters of cancer and birth defects in Argentian. What will be said of this in the future is that one of the most powerful and promising technologies was hijacked and destroyed by unethical entities who used it to enrich themselves instead of using it for public good.

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  2. 2. Kevbonham 3:27 pm 10/23/2013

    @ Dogctor – Pesticide/herbicide use and the resultant toxicity were problems long before GE came around. Those problems in Argentina aren’t because of genetic engineering, they’re because farmers are disregarding regulations around chemical spraying. If those were conventionally-bred crops and they were spraying DDT, would that be any better?

    You say the technology has been hijacked and used unethically, in some cases, I definitely agree with you. But why has all GE been painted with the same brush? What’s unethical about golden rice? How can you claim the creators are trying to enrich themselves when they want to give seeds away for free and allow farmers to continue to propagate it themselves?

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  3. 3. dogctor 3:43 pm 10/23/2013

    What’s unethical about Golden Rice is that it is highly unlikely to ever be useful in treating Vitamin A Deficiency, because a study funded by Bill Gates demonstrated in 2004 that Vitamin A enriched rice is not as effective as far less sexy alternatives. The millions spent to develop it could have been used to actually prevent pain and suffering instead of being wasted on a techno-fix.

    The problems in Argentina is a direct result of a failed concept of creation of herbicide-resistant crops that lead to rapid evolution of resistance, very analogous to abuse of antibiotics, which unlike judicious use, leads to evolution of multi-drug resistant antibiotics.

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  4. 4. Kevbonham 4:03 pm 10/23/2013

    So probably, it would have been better for the defense department not to spend money developing the internet, because for the same amount of money they could have installed more telephone lines, and opened more post offices, which would have been better for the goal of connectivity? It would have been better for the Wright brothers to spend their money laying down more rail lines?

    Linking GE to antibiotics is actually making my point as well. If you use antibiotics improperly, you cause problems. Because of this, should we not use antibiotics?

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  5. 5. dogctor 4:06 pm 10/23/2013

    Sorry -meant to say multi drug resistant bacteria,such as MRSA in pigs and community acquired MRSA. (not multi drug resistant antibiotics).

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  6. 6. dogctor 4:11 pm 10/23/2013

    No we should use antibiotics judiciously, rather than using them irresponsibly sub-therapeutically for growth enhancement on billions of animals. The concept is exactly the same for herbicides used pre-emptively on millions of acres, instead of scouting fields and using herbicides “therapeutically” when and where needed.

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  7. 7. pvincell 4:44 pm 10/23/2013

    It may be of interest to some readers that GMO traits can actually result in improved safety of corn to humans and livestock. See

    Paul Vincelli
    University of Kentucky

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  8. 8. Kevbonham 5:16 pm 10/23/2013

    @ Dogctor – exactly! Judicious use of a technology beats irresponsible use of the technology. Glad we agree :-)

    Let’s restrict bad behavior. Let’s regulate to ensure safety. But let’s do it fairly. If you want to get better regulations for new strains of crops, awesome! But make that apply to ALL new strains, not just GMO strains. Want to regulate pesticide/herbicide use? Makes sense to me, but make regulations apply to all herbicides/pesticides, not just glyphosate.

    We clearly need to fix agriculture. There are a lot of things that need fixing, and GE might be a good tool in that tool belt. But reactionary resistance to any and all GE on principal just because of the tech makes no sense.

    @ Paul – thanks for the link!

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  9. 9. dogctor 6:45 pm 10/23/2013

    Hi Kevin. Its a pleasure to “see” you again.
    But make that apply to ALL new strains, not just GMO strains
    I think what is troubling about with this approach to testing and regulation is that each technology has its own different levels of risk and benefits. So by requiring the same level of testing and regulations of crops known to be low risk, you will be expanding resources needlessly.

    If you look at page 4 of NRC, risks of various techniques were elegantly illustrated as of the date the document was written.

    What isn’t on that list are newer targeted technologies: ZFNs, TALENs, and CRISPR/Cas-based RNA-guided DNA endonucleases, which are programmable and site-specific nucleases that carry different risks than mutagenesis or biollistics. There are others as well discussed in China that @KevinFolta can tell you more about.

    Moreover, if crops were engineered in the past with mutagenesis (wheat and rice)considered risky- doesn’t it make sense to take another look at those crops anew even though they are deregulated?

    I really am not smart enough to give you answers, but I think testing and regulation has to be done on a case by case basis as most things in life. It may diminish as the technology evolves and is refined.

    I hope that makes sense. Thanks for your graciousness. I appreciate it, and have to go do surgery on a little wiener dog now.

    Thanks Dr. Vincelli. That was a great read on b.t. crops.

    Take care for now.

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  10. 10. Kevbonham 7:41 pm 10/23/2013

    I think the phrase “known to be low risk” is key in your analysis. I think we know the techniques used in current GMO production is low risk, or at least as low-risk as mutagenesis breeding. You’re right that new genome editing technologies are untested, and maybe we should include a stronger testing regime on newer technologies to ensure safety. I’d be on board with this. But once the technology has been proven, what then?

    I’d also like to note that none of your comments here did addressed GE technology itself, just specific uses of GE. Is there any use of GE that you would be on board with? Why or why not? Your objection to golden rice was that it’s not efficacious enough. OK, what if it were. Would you be OK with it then?

    Thank you for YOUR graciousness. It’s clear you’re a well-informed and thoughtful person, and your comments always reflect that, even when we disagree (which I grant is most of the time).

    Good luck with the Wiener dog, I’m sure (s)he’s in good hands :-)

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