We Are What We Eat: The History of Humans and DNA

 The Malthus Problem

Almost everyone reading this will have had somewhere between a great grandparent or great great great grandparent who was alive when Darwin went on his legendary trip to The Galapagos Islands in 1831.

People think Darwin came up with the idea for evolution on that trip, but the reality is that the theory predated his birth. What Darwin is famous for is a revolutionary new way of thinking about that idea.

In 1798, Thomas Malthus (of Malthusianism fame), figured out that the productivity of agriculture also meant a rise in the birthrate. On a finite planet, understandably, he could see no way that our food supplies would be able to keep up with our increase in population. The more we had to eat the more we had children and the math was not adding up to good news.

This was a surprise because people back then saw the world the same way a lot of people still see it today: they believed that nature was growing toward a kind of perfection, like a tree reaching for the light with humans right at the top. But what did it mean if food security–humanity’s greatest success–was also our greatest threat? Then what did it mean to be successful if success could kill you? Just what light was this tree of nature striving toward?

It was in answering that question that Darwin had his big realization.

 

Darwin’s Genius

Most people saw evolution the same way most people understand the idea of so-called pesticide-resistant ‘superweeds.” Most people imagine the weeds as nature mutating around our efforts to control them. They imagine the plants actively changing in pursuit of survival, which means they imagine that the phrase survival of the fittest means the ‘survival of the smartest and strongest.’

Darwin saw it for what it really was: animals and plant species sought life, but they weren’t striving to survive–they cannot imagine their future. Their subtle variances simply meant that some simply do survive. Having no foresight, all plants just do what they do, and are what they are, and sometimes their conditions are favourable to their survival and other times they are not, which is why 99.9% of species that have existed have gone extinct. Even with species, time eventually wins. If you’re a thirsty plant during a drought your gene combination will not go forward.

Rather than nature being a tree reaching upward in search of ever and ever brighter light, Darwin’s big insight was that nature is simply a bush filled with so many lottery tickets that at least some forms of life are bound to win.

Humans are not outside of that quality of nature. While we’re all enormously alike, parents are always mixing DNA that has never been mixed before. Sometimes mutations or the mixes themselves create diseases or weaknesses that kill or weaken us. Other times we are one of the few genetically lucky lottery winners to survive The Spanish Influenza, or, if we’re a weed, survive a farmer’s herbicide. There are no super-weeds, or super-people, there are simply weeds and people that best suit the conditions they happen to be in.

Of course, winning this genetic lottery means that the surviving DNA gets to breed more of the following generations. Taking that idea in the opposite direction; Darwin realized that it meant that every living thing was somehow derived from a common ancestor.

Churches at the time found that idea threatening because it created a scientific form of slow-motion creation over which they had no authority. But for science it was a slowly-evolving eureka moment. To them the notion wasn’t dispelling creation, it was seeing it more deeply. 50% of the chemical actions within humans are shared with bananas. That fact does feel like a miracle. And it adds a whole new meaning to you are what you eat.

Of course none of this explained the mechanism by which nature accomplished these variations, nor could we know that the answer might resolve Malthus’s concerns about population.

The Discovery of Genes

Fortunately, a short time later, in the 1840’s, a meticulous scientist and monk (that was common at the time), was in the Czech Republic breeding pea plants. Mendel crossbred tens of thousands of carefully prepared plants and looked at the results. Over time and repetition he realized that there were both dominant and recessive traits that he could predict in subsequent generations.

Mendel was the first person to even imply the idea of genes–the mechanism by which Darwin’s lottery could be held.

By 1869 we had invented technology that would allow us to look at living things more closely. That’s when a Swiss scientist named Miescher saw something in the nuclei of cells. He even wondered if it could explain Mendel’s heredity mechanism but at the time no one saw much value in what would come to be known as DNA and RNA.

DNA was pretty simple stuff, made from an nucleotide alphabet of only four letters. But each of our cells contains about two meters of it. And we have over ten thousand trillion cells. That’s literally about 20 million kilometers or 12½ million miles of DNA! If nature’s bothering to create all of that, there’s a reason. But what? It’s only made of four nucleotides. What could you possibly create with a four letter alphabet?

 

The Colour of Chromosomes

Chromosomes were discovered in 1888 primarily by a German named, Boveri. They got their name because they were really good at absorbing dyes, which makes them easy to see under a microscope (when a cell is dividing). Boveri links them to the idea of heredity but it’s the 1900’s before anyone else really studies them in an effective way.

Thomas Morgan is why so many people associate fruit flies with science experiments. The flies bred quickly so they were perfect for studying how chromosomes might be affecting heredity. He did for the flies what Mendel did for the peas. Thanks to a mutated fly with the wrong coloured eyes, he was able to track inheritance to the point where many scientists were prepared to work from the assumption that chromosomes and DNA were in fact somehow involved in heredity. Morgan won a Nobel for his work with the flies, but even 30 years later there were still a lot of people who did not believe genes existed or that DNA was all that important.

It was about 110 years after Darwin’s voyage on the Beagle, near the end of WWII in the 1940’s, before a Canadian named Oswald Avery managed to change a bacterium by intentionally introducing a trait from a different bacteria’s DNA. That experiment very cleverly proved to everyone that DNA did in fact explain heredity and there were many who felt Avery deserved two Nobel’s for it.

The Shape of Things to Come

Now the race was on to explain DNA’s structure so we could understand how it does what it does. If they could figure out the shape of a DNA molecule they could figure out what it was doing. It was like trying to figure out how the pieces bolted together to make a bio-machine that made…us.

Many expected the brilliant Linus Pauling to be first the one to figure it out, but maybe knowledge acted as a form of blindness. The people who found it were fairly unlikely and they had come from a background of working on military weapons. Crick of the famous Watson and Crick didn’t even have a doctorate at the time, although his effort to get one would play a key role.

Watson was like a Doogie Howser character–a child genius who had been a member of a popular radio gameshow. The problem was, he wasn’t super-familiar with chemistry, and yet their job was to figure out how that little four-letter alphabet could be assembled into life. You can see why it seemed incredible.

Maurice Wilkins is an often-forgotten Kiwi who did a lot of the less glamorous work in developing X-Ray Crystallography that lead to the ability to take images of DNA. That was clearly going to help because at the time everyone was following Pauling’s lead, so they were working from the assumption that the DNA molecule’s shape was a triple helix.

 

The Woman Who Saw Things Clearly

Rosalind Franklin was the woman who figured how to actually take those pictures, but it was a student of hers named Ray Gosling who took the now-famous Photo 51. Gosling ended up being moved to work with Wilkins, who really shouldn’t have unilaterally showed those images to Watson and Crick. But, having seen it, they could now get their G’s C’s T’s and A’s into a double helix that caused Watson and Crick to entirely re-think what they were doing.

Soon after, Franklin wrote a report on an even more detailed photo. That got passed from group leader to group leader at Cambridge until it eventually found its way to Watson and Crick. Using some impressively complex math developed for Crick’s PhD thesis, the two men now used Franklin’s measurements (without her knowledge) and Crick’s math, and they got it all lined up in such a way that it did produce the proteins that combine to form every living thing. Eureka, as they say.

(You can actually help science by playing an on-line game called Fold it where you fold proteins in ways that can help science and humanity. They even get papers into respectable Journals like Nature.)

Franklin went unmentioned for the Nobel because applying complex math to a photo is easier than learning complex math to apply to a photo. But had they not beat her to the solution she would have got the answer shortly thereafter, and she was still the first person to realize that our DNA forms the subtle variances required to ensure our unique genetic codes.

There was a lot of sexism at the time and that likely played a role her being overlooked, but In the end even Watson, who had treated her quite badly, admitted so, and regretted that she had died shortly thereafter, preventing him from making proper amends. And of course the Nobel Prize is not given posthumously….

As for the DNA itself, once it was solved it looked easy. The verticals on the DNA ladder are a sugar. The rungs are the nucleobases we need to make the proteins that fold to make us (drug-based gene therapy is when a drug refolds an improperly folded protein). The rungs always have G with C, and T is always with A (unless it’s RNA then the T is replaced with a U). It’s quite simple chemistry if you’re a chemist.

In a much more recent development, in the spring of 2018 we confirmed a 1990’s theoretical discovery, meaning we also now know there is also i-motif DNA, which is a four strand knot or loop of (C)ytosine to (C)ytosine rungs. (There’s also A, Z, Triplex, Cruciform and G4 DNA shapes, but even scientists don’t know much about what’s going on with those yet, so if you can’t comprehend those you’re in extremely good company.)

After Crick, Watson, Wilkins and Franklin, the next significant person in our understanding of DNA was the South African, Brenner, in 1960. Brenner figures out that gene DNA is transcribed into messenger RNA in a process called transcription. The translated mRNA transports the genetic information from the cell nucleus into the cytoplasm, where it guides the production of the proteins, which make our cell run.

By 1972 a Belgian named Walter Fiers figures out that the parts of our DNA that makes proteins are the genes. Genes are the sections that make the proteins that combine to make us. Shortly thereafter, Herbert Boyer, Stanley Norman Cohen and Paul Berg are the first ones to intentionally transfer a gene. It’s so unique it gets the bacteria to create foreign protein, proving the genetic engineering is possible.

Then Marc Van Montagu and Jeff Schell find a little circular piece of DNA outside the chromosome of Agrobacterium tumefaciens. In nature it put tumours on trees, but they suspected it could facilitate gene transfer between species in nature. By the early 80’s they’ve worked the Americans and the French to create the first genetically engineered plant, a variety of tobacco.

By 1974 Rudolph Jaenisch proves it’s possible by to engineer a mammal, creating the first mouse. That incites a huge shift in medical research because now it’s possibly to do experiments on exactly the same mouse over and over, which is very helpful.

Enter Craig Venter in 2000. He and his team map the entire human genome. Tech means many plants and animals genomes are also getting fully mapped. Diseases are discovered relating to mistakes in copying the code.

By 2012, Jennifer Doudna and Emmanuelle Charpentier, only the second and third woman in the bunch, make maybe the most practical discovery in genetics. They figure out how to use a technology called CRISPR, to use nature itself to edit or patch genetic code. It’s so natural that if you use it to create a new food it isn’t even considered genetically modified because it comes about the same way that nature does it. That takes us to where science is today, but how does DNA actually work?

 

Cell Splits, DNA Snips and Cancer

When your cells split your 2 meters of DNA comes unzipped in the middle. But because it’s a code where the same thing always links to the same thing, in about a second you have made a new piece of matching DNA. You do this a lot with your colon cells because they only survive a few days, skin cells maybe a month, and like pretty much all cells, the liver cells get replaced constantly, but each individual one only replicates about once every 11-17 months. We have about 50-100 trillion cells and about 300 million die every minute, so it’s therefore easy to see why we’re often tired when recovering from surgery. Our body is necessarily very busy.

For the most part that process goes extremely well, but it is possible to have a split go slightly wrong–a wrong letter gets in the wrong place. Biochemists call that a snip. Snips are how you get mutations that can sometimes give you cancer, and that’s why older people get more cancer. They’ve simply had more time for more splits and snips. You can also see why skin or colon cancers would grow much faster than liver cancer, yet snips are also what makes each of us just unique enough that some of us survive The Spanish Influenza pandemic while others do not. A snip was Ethan Hawke’s advantage in the film GATTACA, so named for the four nucleotides in DNA.

Too much snipping and we die. Too little and we never evolve. Our existence literally balances on the peak between those two opposing concepts, hence our interest in genetic engineering.  It’s like tipping the balance in our favour, and now we also tip it in nature’s favour overall, which is why we don’t need baby cows for rennet, horseshoe crabs for the antibodies in their blood, or pigs for insulin.

Conscious Modification

Once we understood that the genes were made of chunks of DNA that simply coded for proteins, we realized that the Natives who turned teosinte grass into modern corn about 10,000 years ago were doing a valuable (yet blindfolded), form of genetic engineering.

On a modern level, despite the fact that Darwin had pointed out that we are all descended from one species (about 3.8 billion years ago), scientists were still surprised when they started noticing that the genes that made a mouse eye for a mouse would amazingly make a fly’s eye on a fly. Before they knew it the scientists realized they–and we–share about 60% of our code with flies! We even have the genes for a tail, that gene just isn’t switched on. It’s both unifying and humbling in a way. We all have the same interchangeable LEGO, we just build different things with it.

Eventually we also learned that it’s not just scientists who move mouse genes into flies, nature also has genes move between species, as they did when an agrobacterium inserted the DNA required to create the sweet potato. Humans are all about 8% virus DNA.  That re-proves that nature sees DNA as a universal code, not one that’s species-specific.

Since all cells DNA carry the instructions for the entire person we had to find hox genes before we understood that something was directing the DNA to become various parts of a plant or animal.

Today, with the help of supercomputers, we can map out the genome of things very quickly, and we can also imagine what would be created if you mixed things that haven’t mixed yet. We know what the codes do in the plants we improve. They are beneficial changes that nature could have done, but we might have all starved waiting for nature to randomly stumble onto an answer that would create more survivable conditions for humans.

Those accurate computer models allow scientists to avoid wasting time on a crop that they can figure out won’t survive, or might be allergenic, etc. That gives them more time to develop the plants that are fit to be food. If that seems unnatural, remember, Darwin didn’t actually use the term survival of the fittest to describe evolutionary success–he simply described it as, descent through modification. Genetic engineering is merely conscious modification.

 

Working With Nature

When a scientist makes a crop that has an “insecticide inside it,” the insecticide is bacillus thuringiensis. It’s bacteria commonly found in soil and it’s what organic farmers spray on the crops because they can’t use the GMO BT strains that have the DNA coding to make the BT within the plant itself.

BT is part of nature, but it’s a part of nature that makes very specific bug’s guts explode. That’s not dangerous for people for much the same reason that your mother doesn’t have to be afraid of Tiger Lilies but she should keep them away from her cat. What can kill one species can be irrelevant to another. But both the BT and the Tiger Lillies are natural, and BT is an example of science using genetic engineering to protect beneficial insects.

Can humans make mistakes? Yes. They do so quite regularly. But on important things we do a lot of double checking, and our food has never undergone more testing. We continue to get things far more right than wrong, and genetic engineering has been precise enough for long enough that it is now proving it can generate substantial gains for humans and our environment.

Far from being afraid of the manipulation of DNA, we should see nature as Darwin’s lottery, with mostly losing tickets; whereas genetic engineering permits the wildness of nature to exist while also allowing us to recognize and define the paths that farmers will need to take when it comes to growing the crops that will sustainably feed a growing world.

Which brings us back to Malthus and his math problem.

Malthus Meets the Green Revolution

What Malthus could or did not include in his calculation were human things like mechanization, plant breeding, The Green Revolution (created by plant hybrids and nitrogen fertilizer), as well as advances in soil science, genetic engineering, and satellite-aided precision agriculture. He also didn’t know that education would lower birthrates, which means the population will actually start dropping to a sustainable level in about 2050.

As recently as 1968 people like Paul Ehrlich were making Malthusian predictions that hundreds of millions of people would be starving every year by the 1980’s. That obviously didn’t happen. In fact there are fewer starving people than ever before, and most of those are due to war, not the failings of agriculture.

 

A Rationally Optimistic Future

We cannot move forward in ignorance and fear. Our future depends on us proceeding forward with the inventiveness contained in Rational Optimism. We must be realistic, and yet at the same time we must take what we learn about nature and use it to help both ourselves and nature.

We cannot do our best for the environment, for our nutrition, or for feeding the world if we don’t use all of the tools that science has discovered on its march through time, whether that’s a Native putting a fish for nitrogen on a corn seed 5,000 years ago, or a geneticist helping a plant develop drought tolerance. In agriculture and in life in general, humans are simply using what they know in the most productive ways they can find. Our knowledge of DNA, coupled with the love of nature that lead to the existence of the sciences, will all be absolutely key to us succeeding in sustainably feeding a growing planet.

 

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