Teeny-tiny deities

 kw: book reviews, nonfiction, genetics, recombinant dna, gene editing, ethics, morality

When I saw the title of As Gods: A Moral History of the Genetic Age, by Matthew Cobb, I knew I was in for a bit of preachiness. I was right, but it was worth it. Dr. Cobb has been among those in the forefront of genetic research for several decades. His perspective is unique. His moral perspective is also nearly unique, as he reports. Few can keep their integrity: As is usual with us faulty humans, when something gets big, really big, you can ferret out nearly every motive by keeping in mind, "Follow the money." There's enough potential money involved that whole national political attitudes have been shifted, repeatedly. I am politically unwise, so I'll leave it to you to read the gory details; I'll look at the technologies he presents us.

The book traces the history of genetic modification, including the dreams of those who, before the ink was dry on Watson and Crick's publication of the structure of DNA, began to opine rapturously about "rewriting the code of life". The predictions of "what we can do with DNA" exceed even the rhapsodies of those promoting "artificial intelligence". I see these two realms of technology running in parallel, a neck-and-neck race for general godhood on both fronts.

Let's look at the current situation first. The present culmination of all the technologies called "genetic editing" is the precise removal and replacement of a single nucleotide, an advance called Base Editing. It's a step beyond the more familiar CRISPR (more below). Versions of this called Prime Editing and Double-Prime Editing are being worked out at present. These technologies still need to go through a number of medical and regulatory hoops before they can be used for therapies, but they are the most promising to date.

CRISPR, when it appeared a decade ago, and garnered a Nobel Prize for Drs Jennifer Doudna and Emmanuelle Charpentier in 2020, was called "DNA scissors". I describe it a little more here. Once the CRISPR agent latches onto DNA, a CAS protein (CAS9 is best known) cuts both strands, and related molecules add "new stuff" at the break and the knit it back together. In more recent years it has been found that the agent isn't as specific as was first thought, and that multiple trials are often needed to get the result you were after. That makes it too risky to use for editing the human germline (the sex cells that turn into babies). Base and Prime Editing methods need a great deal more research and testing to make sure they are as reliable as we need.

However, these targeted mechanisms are a great deal better than older methods, outlined in the book, including something called TALEN, which I liken to a moderately-well-aimed axe. A TALEN needs less accessory machinery than CRISPR and its descendants, because the aim is to remove the "bad half" of a DNA double strand, and let cellular machinery patch the break with a copy of the opposite, "good" side.

Let us consider, though, that methods such as TALEN and earlier tools are not totally obsolete. A proverb of mine (from the Computer Science arena) is, "Nothing is obsolete if it does something you want done." Nature typically takes the "If it isn't broke, don't fix it" approach; our bodies are full of remnants of older structures that work well enough that evolution hasn't removed or replaced them. Think of the appendix; its function has been largely superseded by the spleen, but is still does a couple of immunological functions well enough that we still have it. It is worthwhile keeping, even though we can live without it (mine is gone, 20 years past). Other animals with a less-developed spleen have a much larger appendix. Irony personified: "appendix" means "added on" or even "useless". It isn't.

"Recombinant DNA" is now considered old hat. The technology is more than forty years old. Millions of diabetics are alive because nearly all the insulin they need is produced by this technology. Before recombinant insulin was economical, an eye doctor prescribed insulin drops for my eye, to heal an injury. It was pork insulin, and I was allergic to it; I almost lost the eye. This is the real "Frankenstein" method, where DNA from one organism is spliced into DNA from another. 

Every time a new genetic technology was developed, it was both hyped and decried. Purple promises abounded in medical literature and the popular press, and accusations of "acting like God" abounded right alongside them. On four occasions, lovingly detailed by our author, the researchers have come together and slowed things down. Though they have never called for a moratorium (the "m" word, to many of the author's colleagues), perhaps at least temporary moratoria ought to have been urged. The researchers may not have gone far enough, but the fact that they went as far as they did, and four times, indicates the moral quandary in which they found themselves. 

One side aspect of CRISPR (I think  I have this right) is the Gene Drive, which produces a kind of non-Mendelian inheritance that can drive a species to extinction, either by eliminating all the males or making them all sterile. The mechanics of XY chromosome systems makes it easier to target males. The appearance of this technology led to the closest thing to a moratorium, but eventually, this did not come about. As it happens, a Gene Drive isn't the magic bullet. Limited tests had some early success followed by reduced effectiveness of the Drive. It isn't 100% effective (is anything?). Thus, there are a few survivors. They sire a population that isn't affected by the Gene Drive, and pretty soon the pest (such as a mosquito) you were trying to eradicate returns in a more resistant form. But suppose you did drive a malaria-bearing mosquito species to extinction, worldwide: How likely is it that another species will take its place? Will the replacement be better, or perhaps worse?

If a Gene Drive were developed that affected the human species, then what? There are some folks, often called "environmental wackos", who think the Earth is better off without humans. If a few of them get their hands on a few million dollars, what's to stop them from producing, and then releasing, such an agent? Could its progress be stopped? "Playing God" works both ways.

I find I haven't said much about AI, though I intended to. Similar noise abounds around AI as a doomsday technology. But I think I don't need to say more at this point. Mark Twain wrote, "The reports of my death are greatly exaggerated." So are the predictions of imminent human extinction by DNA or by AI, and also the utopian fantasies regarding both.

A quote near the end of the book sums up a lot of this very well, as told to the author by Sheila Jasanoff:

I think that the fears, the nightmares, serve their own purpose. They are prods to make people think harder about the things that can go wrong. If the 'hope people' are the warriors, then the 'fear people' are the worriers. I think we might need both of them in society, to keep the one calibrating the other, and in some kind of balance.

Although there are those who really wish to exercise godlike powers, it's ironic that the best anyone can so far do is make tiny changes—one base here, half a dozen there—to a DNA library with several billion. A real God, for those who believe in Him, made all of it, all at once.

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A bit off a quibble as a postscript. A chapter titled "Weapons" describes several kinds of what are called "gain of function" research, and mentions several viruses, including a variant of Smallpox, that were made many times more virulent than the "natural" product. But the author goes out of his way to say that the SARS-Cov-2 virus that causes COVID-19 was not produced this way, stating "there is no evidence of this". He has believed a lie. I do not attribute falsehood to Dr. Cobb, but naivety and foolishness. A very few facts:

• Dr. Fauci is known to have responded to a Federal moratorium on gain-of-function research by going around the regulations to funnel several million dollars to the Wuhan Institute of Virology to carry out such research on coronaviruses. (This is usually called money laundering)
• He and others said for a long time that the virus came from a bat bought at a "wet market", and later that it came from a pangolin. The Wuhan wet market does not have either bats or pangolins for sale, not now, and not in 2019. (Yes, I have sources in China)
• He has more recently said that there may have been a "lab leak".
• One of the doctors at the Wuhan lab published several articles, including in Nature, about gain-of-function research on coronaviruses collected from bats a few years previously.
• Thousands of Wuhan residents took vacations in the US and other Western countries in mid-to-late 2019, before the Chinese government announced anything about a new respiratory disease erupting in the Wuhan area. This "pulse" of Wuhan-resident vacationers was unusual. It was followed by the first "pulse" of COVID-19 cases in the West.

I conclude that there was a lot more involved than a "leak" from the Wuhan lab. It is a near certainty that the first genetically-engineered bioweapon has already been used. In folklore, the "bad gods" such as Loki always seem to get their licks in first, and are just barely overcome. Human gods are no better, and typically far worse.