On Oct. 16, 1975, 3-year-old Rahima Banu of Bangladesh became the last human infected with naturally occurring smallpox (variola major). When her immune system killed the last smallpox virus in her body, it also killed the last such smallpox virus in humans. In what is arguably mankind’s greatest achievement, smallpox was eradicated.
Our war with this smallpox virus was brutal. It appears likely that the virus killed about one billion of us. Initially, our only defense was our immune system, but eventually we developed new tools, including vaccination. In the late 1950s, the World Health Organization began responding to outbreaks by vaccinating everyone in the surrounding area to prevent the virus from spreading. By 1975, we had won.
The smallpox virus had only a single host species: us. Other viruses have multiple hosts. For example, some strains of flu live in both humans and pigs, hence “swine flu.” If smallpox had had a second host, eradicating it in humans would have been of little value, since it would have thrived in its second host and later re-emerged in humans.
A few samples of the virus are still kept in special labs: one in the United States and one in Russia. We don’t bother vaccinating against smallpox anymore; if the virus escapes from one of these labs, the war will begin again. Currently, there is debate about whether these samples should be destroyed or kept for scientific purposes.
But the debate should be broadened. Even if we destroy those samples, the war is not over; the smallpox virus has now found a second host. It is not the pig. In fact, it is not even what we think of as a living thing. It is the computer.
This is not some conceptual game. This is real and life-threatening.
If you search online, you can find the sequence for the smallpox genome. It is a word written with the letters A, T, C and G. The word is about 185,000 letters long. It is the word that tells cells to make smallpox viruses. The sequence was stored on a computer in the early 1990s, when a research team led by J. Craig Venter obtained it using a biotechnical process applied to a sample of the virus.
Of course, a word in a computer file cannot kill you. Well, yes and no. In the 1990s, I ran a biotechnology laboratory. In my lab there was a machine much like a soda dispenser, only in this case the reservoirs were filled with chemicals. If I typed in a short word of my choice using the letters A, T, C and G, the machine would squirt one chemical after another into a test tube. When it was done, the test tube would contain trillions of molecules of DNA. Each would look like a necklace, with molecules of adenine, thymine, cytosine and guanine (the building blocks of DNA) strung according to the word I had typed.
At that time, the 10,000-letter sequence of the H.I.V. genome was available online. I contemplated using my machine, together with well-known biotechnical methods, to create, de novo, the H.I.V. genome — an actual molecule identical to that found in H.I.V. viruses living in the wild. I had reason to believe that inserting such a synthetic molecule into a living human cell would cause the cell to manufacture full-blown H.I.V. viruses that could then be transmitted from person to person and cause AIDS.
I decided not to do the experiment, but I began to worry. If I could do it, so could others with high-tech labs.
Which brings us back to smallpox. Might someone resurrect it? You may think this is mere speculation, but in 2002, scientists used the approach just described to produce an infectious polio virus. It is possible that the great labs, with great scientists, the best equipment and substantial funds, could overcome the considerable challenges that exist and resurrect smallpox right now. Before too long, more modest labs may be able to accomplish the same thing.
I am worried, but also amazed. Smallpox has miraculously and unconsciously saved itself through an extraordinary act of evolution. After thousands of years, it was on the verge of extinction; it existed in one small girl, and just before that girl’s immune system killed its last living member, a sample was taken and stored in a lab. Years later, that sample was used by another lab to sequence the viral genome. The sequence was placed on a computer, infecting a new “species” that had just come into existence.
Do we sit and wait for the day when someone releases resurrected smallpox on an unvaccinated world? I’m a scientist, not a policy expert. But would it be wise for us to consider limiting the distribution of the tools of this emerging technology?
Leonard Adleman is a professor of computer science and molecular biology at the University of Southern California.