Corn Star

What I learned from the prophetic humility of Barbara McClintock

Nobel Lauriate James Watson, “It's really that science caught up with Barbara.”

It’s high summer, or at least it was when I started to write this note to you. And ignoring the fact that where did summer go, and that I had to take a two-week vacation from writing to focus on not really doing anything, I really do want to tell you about corn.

This is not the Michael Pollan-we-are-all-consuming-way-too-much-corn story. And not the memories-of-my-verging-on-prepper-grandparent’s-rustling-cornfields-deep-in Michigan-farm-country story either. And its not (at least for now) really a story about how to make ink from juice made from the black corn of the high Andes or the purple corn used as a dye by the Hopi nation. Although I really do want to try that. No. This is a story about a scientist born in 1904 who spent most of her life in relative obscurity looking very carefully at corn kernels and whose revolutionary methods are still reverberating today.

Above is a photo of my hero, Barbara McClintock, discoverer of the jumping gene and radical pioneer of fluid genetics. That’s her in the middle of the frame wearing dark blue pants sensible shoes a turquoise sweatshirt and a grey field jacket surrounded by a flurry of reporters. The reporters are there because, at 81, she’s become the first woman ever to be awarded an unshared Nobel Prize in Physiology or Medicine. She’s just outside of her lab at Cold Spring Harbour New York where she worked in relative obscurity for most of her life. She is not particularly avoiding the cameras but rather than giving an interview she is walking determinedly across campus to harvest black walnuts from the local trees. According to her collegues, McClintock would crack the walnuts open by driving her Honda Accord over them. She was famous for her black walnut cake and black walnut brownies. I found a picuture of the cake but no recipe on Facebook. The black walnuts alone were enough to win me over.

Here is a picture of Barbara McClintock with the tools that she used her whole life. Microscope, tweezers, petri dish, stain, and somewhere in there a slice of a kernal of corn that she grew and harvested from scratch. This was before X-ray crystalography allowed researchers to see the double helix shape of DNA, and before supercomputers could map out the sites and functions of individual genes. Then, as now, corn was not considered a particulary glamourous or groundbreaking field for study.

This is a bit of an aside, but here is a kind of similar picture of Rosalind Franklin who worked for years with her students to produce a very famous picture using X-ray cystalography.

Here is the famous picture. It’s known as photograph 51 and was taken by Raymond Gosling, Franklin’s research assistant in the basement of the Biophysics Unit at King’s College London in May 1952. The date is significant because that year it was shown to Dr. James Watson (without her permission or knowledge) and, not long afterward, Watson claimed that the moment he saw it he realized that DNA must be a double helix shape without citing Franklin’s earlier work and lectures on the probable helix-shape. The image was central to the final picture we have of DNA which would win Watson and Crick the Nobel Prize.

The writer and eminent physicist, J.D. Bernal would describe photograph 51 as “the most beautiful X-ray photograph of any substance ever taken.” The image captured clearly, for the first time, the basic building blocks of every living thing. It was a year and a half later, on 28 February 1953, that Crick announced dramatically in the Eagle pub that he and Watson had found the secret of life. The modern plaque (below) at least references Franklin:

Here is another picture of Rosalind Franklin. Before getting to make her case as one of the co-discoverers of DNA (the secret of life!) politics pushed her out of her position at the university. She went on to make major discoveries in the molecular structures of DNA and RNA in viruses, coal, and graphite at her new job, but a few years later, she was diagnosed with ovarian cancer possibly brought on by all of her work with X-rays. Franklin was sometimes called the Syvia Plath of science. She died at 38.

There is some internet debate as to whether Franklin was deliberately shut out of scientific fame, overlooked, or was just more careful and less declarative than Watson and Crick. This quote from Franklin I found on Wikipedia kind of reminds me of McClintock, “We are not going to speculate, we are going to wait, we are going to let the spots on this photograph tell us what the [DNA] structure is.”

But let’s get back to corn. Below is the feild where Mclintock grew her corn at Cold Harbour on Long Island. It is now a parking lot. That could be her, slightly bent over to show some grad student a row of seedlings.

Maybe this the grad student from the previous picture. I am not sure who he is but that’s definitely Barbara McClintock right down among her cornplants bent toward one particular specimen with full body focus. I think it might be my favourite picture of her. The plants are forgrounded and Barbara McClintock’s intenisity is on full display. The professional white dressshirt peaking out of the comfortable nubbly plum-coloured sweater. The sensible grey corduroy pants. The labelled pots. The even, milky light of the greenhouse. The balding collegue beside her looking on with an awe? Just posing for the camera? Whatever the stance it can only contrast with McClintock’s gently steady hands-on intelligence.

The corn she was growing there is L. Mays what we might call maize, Indian or fall corn. But to the expert these ears are like a piano roll— a sequence of coded colours that tell a clear story if you know how to play it.

An illustration of corn kernel specimens, included in Barbara McClintock's article in the 'Cold Spring Harbor Symposia on Quantitative Biology' in 1951 Courtesy of the Barbara McClintock Papers, American Philosophical Society

Corn makes a great test subject. Each kernel is an embryo produced from an individual fertilization which means that hundreds of offspring can be scored on a single ear which makes maize an ideal organism for genetic analysis. Even single kernels are not a uniform colour. The above photo shows some of the strangely beautiful kernals that Barbara McClintock was working with. Because corn is easily cross-bred and cloned, pattens of kernels within the corn and within a single kernal can be traced back to their heredity through successive generations. What was interesting about the pattern of colouration though was that it couldn’t be explained just by hereditiy. At the chromosomal level something else was going on. McClintock recognized that the patterning was not random but the result of a set of genetic triggers.

Below the level of kernel are the individual corn cells. And within the corn cell a nucleus and within the nucleus a tangle of threads that science understood to be the critical component of reproduction. Here is what McClintock and her fellow cytologists were looking at with some of her notes on it. You can kind of see strings of chromosomes and guess that each has a particular effect on the corn plant.

OK, one more aside: For those interested in natural dye and colour I should say that her slides would have looked pinkish-purple, a bit like the above photograph. The color comes from a carmine microscope stain. This is the stain still used today for highlighting cell reproduction and is a derivative of the female cochineal scale insect that intensifies the pigments of the prickly pear into still significant colourant which when combined alum and aecedic acid and bits of iron from her scalpel bonds to the nucleic proteins of plant cells highlighting just the genetic material.

These helpfully numbered squiggles are the ten chromosomes of a corn cell. When Barbara McClintock first started, it wasn’t clear that there were exactly ten chomosomes or what information was held in the various parts of this scribble. This was decades before anyone could envision the double helix or map the genome. It was clear that chromosomes —so named for their ability to hold color!— also held the key to inherited characteristics. By making slight changes in corn breeding or damaging parts of the chromosomes with X-rays and comparing these with corn from the same and related lineages, McClintock was able to actually see what had previously only been observed statistically or theoretically. Certain parts of these strings of protien were directly responsible for passing on a characteristic like red or purple kernels in the next generation. By a painstaking trial and error methods, McClintock was able to visually prove what had previously only been theorized about how plants transfer information.

Where you see the red circles McClintock has noted breaks in the chromosome. It was at these breakage points that she was able to discover something quite wierd. Something revolutionary enough that when she first presented her findings she was met with distain, mystification and a lot of awkward silence. It would be decades before the significance of her discoveries would be begun to be understood and nearly 40 years before they would be awarded global recognition. Science is some ways still working out the possibilities of the paradigm shift that she set in motion.

I am not a cytogeneticist and I only ever took one university-level biology course which I just barely passed, but I have read everything I could find of Barbara McClintock and I think the specifics of her discoveries and method and thinking are fascinating enough that I will try to explain.

Most famously these breaks in the strings of chromosomes represent the beginning of McClintock’s understanding of transposition or what became known as jumping genes. While each part of the chromosome has a different function, the position of individual genes, she suspected, was not fixed but can move around, her proof of this goes to the heart of her Nobel Prize win. She showed that small fragments of DNA which she called transposable elements (or transpons) could move from place to place and in moving turn on or off certain characteristics, and in doing so, control the expression of genes.

But not only were parts of the chromosome broken off —there was a particular part of the chromosome responsible for making that break and recombing the sequence in ways favourable to the whole plant. Genes were moving around not in the random way in the way of a child of two different parents but instead they were responding, evolving even, in real time, to environmental stresses.

Here is a picture of Barbara McClintock accepting the Nobel Prize thirty years after she recognized that those breaks in the chromosomes were controlled, moving parts of the corn genome. Over years and with exhaustive documentation, McClintock was able to pinpoint parts of that mass of squiggles that were responsible not just for particular characteristics but responsible for turning on or off certain characteristics. By carefully documenting the process of cell division in outlier cases, McClintock suggested that some genes were controlling genes. In fact she saw the genome as a wholistic unit capable of adapting over generations and in real time as cells divided, specialized and responded to their environment. That adaptation and mutation could happen within a single generation. The discoveries would lead to at least 3 of the most important current feilds of study in genetics: cytogenetics, epigenetics, and gene editing— which lead to innovations like CRISPR (a sort of natural DNA surgery tool). But it wasn’t just what she learned but how she learned that I find inspiring.

Now this plant has a secret, I’m not going to tell you. You can look at it and see
what you find out.’ —Barbara McClintock

Here is a paper bag for collecting sampless with some of Barbara McClintocks notes on it. Her method was sometimes called feminist or mystical or ahead-of-its-time but I think it was most fascinating for its simplicity. Evelyn Fox Keller, in what is still the best biography of McClintock, explains it like this:

“It was her conviction that the closer her focus, the greater her attention to individual detail, to the unique characteristics of a single plant, of a single kernel, of a single chromosome,” Keller wrote, “the more she could learn about the general principles by which the maize plant as a whole was organized, the better her ‘feeling for the organism.’”

This photo says a lot about her approach. you can see her sample paper collection bags which double as kind of notebook strapped to her belt. And again that body language of sharp focus. Maybe I am imagining it but you can almost see her relating to the corn not just an an object of study but as a subject.

In the archives too are the ears of corn that she worked with still holding their coloured kernals to be re-read by future generations. Her method is so much about watching the growth of the corn plant by plant. Then collecting, labelling and going deep into each kernel into each cell’s nucleus and finding there, not just a family tree but its writhing, adapting roots and new branches.

What she discovered this way didn’t just baffle her contemporaries. Those who understood what she was proposing saw what a shocking perspective her close observations led her to. In her biography of Dr. McClintock, A Feeling for the Organism, her findings were at odds with very nature of Darwinian evolution. The theory of evolution talks about mutations so that changes occur randomly in genes, which give rise to variations that over time prove beneficial or not, and the best mutations survive to form new species better equipped for their environ. Dr. McClintock, on the other hand, was saying that there is a controlling element on the genetic level. That purposeful changes happen in genes. That transposable elements can jump to specific places in response to stress and then insert themselves into genetic material and alter it for future generations.

What she found in corn cells would prove true of all living things. Mobile Genetic Elements (or MGEs) make up about 50% of our own DNA, meaning that 1.5 billion nucleotides of our genome code for mobile elements. To put that in perspective, the protein-coding genes that we think of as the workhorses of life make up only 2–3% of our genome.

In her Nobel Prize banquet speech Dr. McClintock owns the obscurity that afforded her almost monastic devotion to corn, subtly disses all those collegues who didn’t get what she was up to, and at the same time flips the notion of the scientist as discoverer or expert that pries the truth for nature. “It might seem unfair,” she says in a press statement after winning the award, “however, to reward a person for having so much pleasure over the years, asking the maize plant to solve specific problems and then watching its responses.” She did not look to the plants for proof of a theory or hypothesis. She didn’t look to plants to answer her questions. Instead she found that a single grain might act as a guide, leading her to the sorts of questions she should be asking in the first place.

I found that the more I worked with [the chromosomes] the bigger and bigger [they] got, and when I was really working with them I wasn’t outside, I was down there. I was part of the system. I was right down there with them, and everything got big. I even was able to see the internal parts of the chromosomes—actually everything was there. It surprised me because I actually felt as if I were right down there and these were my friends.

Corn ear specimen photographed in 1945 Courtesy of the Barbara McClintock Papers, American Philosophical Society.

Five researchers at the Plant Breeding Department at Cornell University in 1927. Left to right: Charles R. Burnham, Marcus M. Rhoades, Rollins A.Emerson, Barbara McClintock. Kneeling is George Beadle. (note the paper bags tucked into belts CSHL Archives.

I did a bit of digging for pictures of McClintock. The first one is early on in her career in 1927 with her collegues at Cornell. Somehow in all of these portraits you can see in her stance the particular mix of humiltiy and confidence that she brought to her work. She was an outsider but she was not alone. I love that she was ignorred and then the science caught up to her and vindicated what she had been saying all along. I love that that her findings which were built from what looks like a child’s microscope and a cornpatch just seemed to become richer over time. As increasingly technical biology helps us visualize the subtle workings of DNA through electron microscopy, the more obvious it becomes that McClintock’s views where not really maverick but rather closely observed. I love that she loves black walnuts and that she has drawn people’s attention to what galls say about the relationship between bacteria, plants, and animals. I think this quote best defines her approach:

No two plants are exactly alike. They’re all different, and as a consequence, you have to know that difference. I start with the seedling and I don’t want to leave it. I don’t feel I really know the story if I don’t watch the plant all the way along. So I know every plant in the field. I know them intimately. And I find it a great pleasure to know them. —Barbara McClintock

Her methodology and even her choice of subjects reminds me a bit of what Georges Perec calls the infraordinary: “You must set about it more slowly, almost stupidly. Force yourself to write down what is of no interest, what is most obvious, most common, most colourless...Make an inventory of your pockets, of your bag...Question your tea spoons.” Or Georgio Morandi, another pioneer whose beautiful expertise came from narrowing his focus, who says: “One can travel this world and see nothing. To achieve understanding it is necessary not to see many things, but to look hard at what you do see.”

But as down to earth as she clearly was, there is another part of Barbara McClintock’s approach that is just as significant. James Shapiro writes a pretty good essay that takes into account not just how radical her methods of fine-grained noticing were, but how radical those minutae became when fit into a bigger picture.

The second obstacle to broad acceptance of McClintock’s perspective is that standard theories are still framed in terms of independent genetic units. Whereas McClintock thought of the genome as a complex unified system exquisitely integrated into the cell and the organism — Obituary in BioEssays, by James A. Shapiro

I have a feeling that as science begins waking up to the inter-relatedness of all systems and expands its sense of intelligences that go beyond just what humans do, that McClintock’s thinking will look not just precient, but futuristic and necessary. If the chromasomes in corn cells are able to respond to their enviroment by breaking apart and recombining in ways that benefit the whole plant, what might this mean for what we call individual humans?

Increasingly, science is recognizing that our measurement tools are part of the experiment. Science is recognizing that the binaries of male/female human/non-human living/non-living, natural/unnatural are missing out on a whole world of possibilites. Science is recognizing that many of the arbitrary divisions that we have used to understand the world are as obscuring as they are clarifying. When Barbara McClintock observed an ear of corn that she grew from a seed whose parents and grandparents she’d been watching for generations, she saw a pattern, and in the pattern she saw a language like grooves in a record or dots of Braille on the page. Somewhere I read that she was the corn whisperer, but I don’t think that’s quite right, I think it was the corn that was whispering to her. In her radical humility she simply bend down low enough to join the plant on its own level. She waited patiently without judgement. Only then could she begin to hear it.

I want to end with Barbara McClintock’s own words from her Nobel Prize acceptance speech:

“In the future, attention undoubtedly will be centered on the genome, with greater appreciation of its significance as a highly sensitive organ of the cell that monitors genomic activities and corrects common errors, senses unusual and unexpected events, and responds to them, often by restructuring the genome. We know about the components of genomes that could be made available for such restructuring. We know nothing, however, about how the cell senses danger and instigates responses to it that often are truly remarkable.”

Ten things I learned from the genius of Barbara McClintock…