an autodidact meets a dilettante…

The origin of species is a natural phenomenon

Jean-Baptiste Lamarck

The origin of species is an object of inquiry

Charles Darwin

The origin of species is an object of experimental investigation

Hugo de Vries

(quoted in The Gene: an intimate history, by Siddhartha Mukherjee)

Gregor Mendel

I’ve recently read Siddhartha Mukherjee’s monumental book The Gene: an intimate history, a work of literature as well as science, and I don’t know quite where to start with its explorations and insights, but since, as a teacher to international students some of whom come from Arabic countries, I’m occasionally faced with disbelief regarding the Darwin-Wallace theory of natural selection from random variation (usually in some such form as ‘you don’t really believe we come from monkeys do you?’), I think it might be interesting, and useful for me, to trace the connections, in time and ideas, between that theory and the discovery of genes that the theory essentially led to.

One of the problems for Darwin’s theory, as first set down, was how variations could be fixed in subsequent generations. And of course another problem was – how could a variation occur in the first place? How were traits inherited, whether they varied from the parent or not? As Mukherjee points out, heredity needed to be both regular and irregular for the theory to work.

There were few clues in Darwin’s day about inheritance and mutation. Apart from realising that it must have something to do with reproduction, Darwin himself could only half-heartedly suggest an unoriginal notion of blending inheritance, while also leaning at times towards Lamarckian inheritance of acquired characteristics – which he at other times scoffed at.

Mukherjee argues here that Darwin’s weakness was impracticality: he was no experimenter, though a keen observer. The trouble was that no amount of observation, in Darwin’s day, would uncover genes. Even Mendel was unable to do that, at least not in the modern DNA sense. But in any case Darwin lacked Mendel’s experimental genius. Still, he did his best to develop a hypothesis of inheritance, knowing it was crucial to his overall theory. He called it pangenesis. It involved the idea of ‘gemmules’ inhabiting every cell of an organism’s body and somehow shaping the varieties of organs, tissues, bones and the like, and then specimens of these varied gemmules were collected into the germ cells to produce ‘mixed’ offspring, with gemmules from each partner. Darwin describes it rather vaguely in his book The Variation of Animals and Plants under Domestication, published in 1868:

They [the gemmules] are collected from all parts of the system to constitute the sexual elements, and their development in the next generation forms the new being; but they are likewise capable of transmission in a dormant state to future generations and may then be developed.

Darwin himself admitted his hypothesis to be ‘rash and crude’, and it was effectively demolished by a very smart Scotsman, Fleeming Jenkin, who pointed out that a trait would be diluted away by successive unions with those who didn’t have it (Jenkin gave as an example the trait of whiteness, i.e. having ‘white gemmules’, but a better example would be that of blue eyes). With an intermingling of sexual unions, specific traits would be blended over time into a kind of uniform grey, like paint pigments (think of Blue Mink’s hit song ‘Melting Pot’).

Darwin was aware of and much troubled by Jenkin’s critique, but he (and the scientific world) wasn’t aware that a paper published in 1866 had provided the solution – though he came tantalisingly close to that awareness. The paper, ‘Experiments in Plant Hybridisation’, by Gregor Mendel, reported carefully controlled experiments in the breeding of pea plants. First Mendel isolated ‘true-bred’ plants, noting seven true-bred traits, each of which had two variants (smooth or wrinkled seeds; yellow or green seeds; white or violet coloured flowers; flowers at the tip or at the branches; green or yellow pods; smooth or crumpled pods; tall or short plants). These variants of a particular trait are now known as alleles. 

Next, he began a whole series of painstaking experiments in cross-breeding. He wanted to know what would happen if, say, a green-podded plant was crossed with a yellow-podded one, or if a short plant was crossed with a tall one. Would they blend into an intermediate colour or height, or would one dominate? He was well aware that this was a key question for ‘the history of the evolution of organic forms’, as he put it.

He experimented in this way for some eight years, with thousands of crosses and crosses of crosses, and the more the crosses multiplied, the more clearly he found patterns emerging. The first pattern was clear – there was no blending. With each crossing of true-bred variants, only one variant appeared in the offspring – only tall plants, only round peas and so on. Mendel named them as dominant traits, and the non-appearing ones as recessive. This was already a monumental result, blowing away the blending hypothesis, but as always, the discovery raised as many questions as answers. What had happened to the recessive traits, and why were some traits recessive and others dominant?

Further experimentation revealed that disappeared traits could reappear in toto in further cross-breedings. Mendel had to carefully analyse the relations between different recessive and dominant traits as they were cross-bred in order to construct a mathematical model of the different ‘indivisible, independent particles of information’ and their interactions.

Although Mendel was alert to the importance of his work, he was spectacularly unsuccessful in alerting the biological community to this fact, due partly to his obscurity as a researcher, and partly to the underwhelming style of his landmark paper. Meanwhile others were aware of the centrality of inheritance to Darwin’s evolutionary theory. The German embryologist August Weismann added another nail to the coffin of the ‘gemmule’ hypothesis in 1883, a year after Darwin’s death, by showing that mice with surgically removed tails – thus having their ‘tail gemmules’ removed – never produced tail-less offspring. Weismann presented his own hypothesis, that hereditary information was always and only passed down vertically through the germ-line, that’s to say, through sperm and egg cells. But how could this be so? What was the nature of the information passed down, information that could contain stability and change at the same time?

The Dutch botanist Hugo de Vries, inspired by a meeting with Darwin himself not long before the latter’s death, was possessed by these questions and, though Mendel was completely unknown to him, he too looked for the answer through plant hybridisation, though less systematically and without the good fortune of hitting on true-breeding pea plants as his subjects. However, he gradually became aware of the particulate nature of hereditary information, with these particles (he called them ‘pangenes’, in deference to Darwin’s ‘pangenesis’), passing down information intact through the germ-line. Sperm and egg contributed equally, with no blending. He reported his findings in a paper entitled Hereditary monstrosities in 1897, and continued his work, hoping to develop a more detailed picture of the hereditary process. So imagine his surprise when in 1900 a colleague sent de Vries a paper he’d unearthed, written by ‘a certain Mendel’ from the 1860s, which displayed a clearer understanding of the hereditary process than anyone had so far managed. His response was to rush his own most recent work into press without mentioning Mendel. However, two other botanists, both as it happened working with pea hybrids, also stumbled on Mendel’s work at the same time. Thus, in a three-month period in 1900, three leading botanists wrote papers highly indebted to Mendel after more than three decades of profound silence.

Hugo de Vries

The next step of course, was to move beyond Mendel. De Vries, who soon corrected his unfair treatment of his predecessor, sought to answer the question ‘How do variants arise in the first place?’ He soon found the answer, and another solid proof of Darwin’s natural selection. The ‘random variation’ from which nature selected, according to the theory, could be replaced by a term of de Vries’ coinage, ‘mutation’. The Dutchman had collected many thousands of seeds from a wild primrose patch during his country rambles, which he planted in his garden. He identified some some 800 new variants, many of them strikingly original. These random ‘spontaneous mutants’, he realised, could be combined with natural selection to create the engine of evolution, the variety of all living things. And key to this variety wasn’t the living organisms themselves but their units of inheritance, units which either benefitted or handicapped their offspring under particular conditions of nature.

The era of genetics had begun. The tough-minded English biologist William Bateson became transfixed on reading a later paper of de Vries, citing Mendel, and henceforth became ‘Mendel’s bulldog’. In 1905 he coined the word ‘genetics’ for the study of heredity and variation, and successfully promoted that study at his home base, Cambridge. And just as Darwin’s idea of random variation sparked a search for the source of that variation, the idea of genetics and those particles of information known as ‘genes’ led to a worldwide explosion of research and inquiry into the nature of genes and how they worked – chromosomes, haploid and diploid cells, DNA, RNA, gene expression, genomics, the whole damn thing. We now see natural selection operating everywhere we’re prepared to look, as well as the principles of ‘artificial’ or human selection, in almost all the food we eat, the pets we fondle, and the superbugs we try so desperately to contain or eradicate. But of course there’s so much more to learn….

William Bateson