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Authors: Aarathi Prasad

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The year was 1827, and a German scientist, Karl Ernst von Baer, was investigating the reproductive tract of a bitch. It had of course long been obvious that birds and reptiles had eggs; these
were in plain sight. By the seventeenth century, it was suspected that mammals might have them, too, although no one had been able to find one. Leeuwenhoek had searched for a mammalian egg with his
increasingly sophisticated microscopes, but he had thrown off the hunt as a lost cause. Using a better microscope, however, von Baer had been able to distinguish a yellowish-white, point-like
object within some structures, called follicles,
that he had taken from a dog’s ovaries.

Von Baer was curious, so he sliced open a follicle, used the tip of his knife to remove the pin-prick object, and placed it under his microscope. ‘It is truly wonderful and surprising to
be able to demonstrate to the eye, by so simple a procedure, a thing that has been sought so persistently and discussed ad nauseum in every textbook of physiology as insoluble’, he later
wrote of his momentous discovery. He was ‘utterly astonished’ to see the egg with his own eyes ‘and so clearly that a blind man could hardly deny it’. But blind men there
had been aplenty – including Leeuwenhoek.

To Leeuwenhoek, eggs existed so that the preformed embryos in sperm could be implanted in them. His stubbornness is all the more surprising when you consider that in addition to the discovery of
sperm, the Dutchman is credited with the discovery of parthenogenesis, the development of the egg into a new individual being without fertilization by sperm. If you weren’t too sure that eggs
existed, as Leeuwenhoek said he wasn’t, you might say that this process amounts to a female bearing offspring with no lasting input from a male – the equivalent of a virgin birth. And
Leeuwenhoek was the first scientist to notice that female aphids had virgin births all the time.

An avid gardener, in the summer of 1695 he became somewhat concerned that the leaves of his gooseberry, cherry, and peach trees were damaged. At first he thought the mutilations were the work of
ravenous ants, but on closer inspection, he spied aphids. Leeuwenhoek did with the aphids what he did best: he pulled out a microscope and, as had become his custom, he searched for the eggs of
this new species. He found none. He then dissected what he guessed were the females. He found no eggs in them either. But he did find miniature, preformed aphids. The first specimen he dissected
contained four young, and he removed as many as sixty from another.

This should have put an end to the idea that male semen, or sperm, was the sole instigator of new life. But there again, Leeuwenhoek had chanced upon an organism in which
reproduction is by no means straightforward. The sexual tactics employed by female aphids are tricky and complex. Two hundred million years ago, the insects evolved a reproductive strategy that
allows them to practise reproduction by parthenogenesis – in cycles. This means that female aphids do have eggs, and both the fertilized and unfertilized eggs of a female are capable of
forming embryos. The small aphids that Leeuwenhoek observed when he cut open his female – those born live as a result of parthenogenesis – were exclusively female. What is more, a
single female generated by parthenogenesis may contain three generations within her body: the numerous embryos of her unborn daughters and, within them, her granddaughters-to-be in the early stages
of development. For aphids this amounts to a brilliant strategy for rapidly producing an immense population; a virgin female can, in theory, produce billions of offspring in a lifespan of roughly
one month. Here was a stack of Russian dolls, miniature yet fully formed creatures in ever smaller packages, just waiting to be born – a perfect preformed embryo, but from a female.

Despite this finding, and von Baer’s production of the elusive mammalian egg from a dog, the egg continued to be considered the lesser element of reproduction into the Victorian age. In
1849, Richard Owen, who had classified spermatozoa as parasites, delivered a talk at the Royal College of Surgeons entitled ‘On Parthenogenesis, or The Successive Production of Procreating
Individuals from a Single Ovum (Egg)’. Owen had coined the word ‘parthenogenesis’, yet he could not extricate from his mind the influence of sperm over the process. Instead of the
potential of eggs to self-reproduce, his lecture expounded on the virtue of sperm. For him, a ‘virgin birth’ could only
ever follow an original fertilization event
– and fertilization required sperm. What he called ‘spermatic virtue’ was a power contained in sperm that could be divided equally among countless offspring. He told his audience
that the development of an embryo by parthenogenesis differed from a normal fertilization involving sperm ‘only in... non-essential particulars’, by which he meant that the power of
sperm was the absolute requirement.

In the late nineteenth century, Owen would come under fire for this explanation. His critics were formidable – among them Darwin and Darwin’s ‘bulldog’ supporter, Thomas
Henry Huxley. Huxley was professor of general natural history at London’s Imperial College and had contributed substantial knowledge to the growing field of comparative anatomy and
palaeontology. He levelled great criticism at Owen’s science and methods; in return, Owen published cloaked insults about Huxley’s own work. It’s fair to say that their earlier
friendship had dissolved by this time. A colleague of Huxley’s even advised him to shoot Owen in a duel. The two scientists had running arguments on anatomy, aphids, and parthenogenesis.
Huxley particularly attacked Owen’s references to a non-descript spermatic virtue or ‘force’ that could be retained through generations of aphid females, calling such speculations
‘ignorance writ large’. For his part, Darwin egged on Huxley to challenge Owen on this point.

Meanwhile, in Germany another distinguished professor of comparative anatomy, Karl Ernst von Siebold, also ridiculed the belief in all-powerful sperm. Siebold did not respond by producing more
speculation, but by performing exhaustive experiments to investigate ‘true parthenogenesis’. This was, in contrast to Owen’s definition, the development of an egg that was
perfectly capable of being fertilized by sperm but which had not been. For his test subjects, Siebold turned to aphids, bees, and moths. He knew the conviction that eggs must be
exposed to spermatozoa before they can develop was very deeply rooted; he himself had once been a strong opponent of the existence of parthenogenesis.

In 1857, after years of study, Siebold published his findings on bees and Psyche and Solenobia moths; in a nod to Richard Owen, he entitled his text
On a True Parthenogenesis
. In his
exacting observations, Siebold had noted that the unfertilized eggs of his moths produced female offspring, but that queen bees produced male drones through parthenogenesis and female offspring
from eggs fertilized by sperm. Contrary to Owen’s definition, it was clear that new organisms could develop solely from eggs. Siebold also uncovered that not only can eggs develop into fully
formed animals quite without any fertilization event but also that parthenogenesis was by no means an exceptional occurrence, something peculiar to aphids. He made a point of countering the idea
that ‘development of the eggs can only take place under the influence of the male semen’. This age-old concept, he wrote, ‘has suffered an unexpected blow’. Rather than
being a result of some undefined force of questionable existence, parthenogenesis was an independent, fixed, orderly event.

But if eggs could develop on their own, as Siebold had proved, then what was the point of the male? Based on Siebold’s work, Darwin made a remarkable conjecture: ‘I have often
speculated for amusement on the subject, but quite fruitlessly,’ he wrote to his friend Huxley, ‘But the other day I came to the conclusion that some day we shall have cases of young
being produced from spermatozoa ... without [an egg].’ Darwin had a point: if eggs could independently generate life, why couldn’t sperm do it, too? And if not little people, what was
inside the sperm, and how were these seemingly living creatures made?

In 1905, Jacques Loeb provided an answer. Loeb, a physiologist working in Germany, was busy trying to force unfertilized eggs to develop into embryos.
Using alkaline or acid solutions, potassium, and salt, even ox blood and cane sugar, he triggered development in the unfertilized eggs of sea urchin, starfish, marine molluscs, and other creatures.
For the first time in history, someone had managed to create new life in the laboratory with
no sperm at all
.

In working out what to substitute for sperm, Loeb realized he needed to find something that must have two effects on the egg. ‘In the first place’, he wrote, to ‘cause... its
development’ and in the second to ‘transmit... the paternal characters to the developing embryo’. For the marine species with which he was experimenting, the ability to cause the
embryo to develop was enough. Baby sea urchins born in his lab would need no fathers from which to acquire paternal characteristics. The same could not be said if the subject were not sea urchins
but humans.

The fluid praised as the essence of life by Aristotle and Galen (and the innumerable others who came before and after) is indeed remarkable. Human semen is a rich cocktail, a combination of
sugars, salts, enzymes, vitamins, and minerals, including such truly essential ingredients as fructose, sorbitol, inositol, phosphorus, zinc, magnesium, calcium, potassium, ascorbic acid (vitamin
C), and cobalamin (vitamin B12). As the ancient thinkers suspected, it is also the medium through which a father provides his set of instructions for making offspring. But unknown to these early
natural philosophers, some part of semen – about five percent of what a man ejaculates – contains fifty million to two hundred million sperm. These cells are highly specialized, built
to travel up to four millimetres a minute and to release chemicals that can target and penetrate the egg.

The creation of sperm begins inside the testes of a pubescent boy, when the solid cords that had transected these glands
throughout his childhood begin opening up into
tubes. The process carves a space at the cord’s centre through which fluids will eventually be able to pass. These tubes will become contorted and so numerous and fine that in an adult male
testicle, their collective length will measure as much as 350 metres, or more than one thousand feet. They will also become home to the stem cells that become sperm, called
spermatogonial stem
cells
, or SSC. Stem cells are by definition immature, in that they are somewhat undecided as to their identity and therefore retain the ability to become something different – something
more definitive, more specialized. At the start of a wonderfully efficient production line, these rounded cells are the first widgets in the manufacture of mature, tadpole-like sperm and,
ultimately, are the basis of male fertility. Each sperm is moulded out of the contents of these stem cells, then conveyed into holding areas, a bit like reservoirs, which line the outer layers of
the fine tubules that now populate the testes. Driven by the male sexual hormone, testosterone, developing sperm will move in waves of output along the belts of these tubes, which eventually spiral
like a corkscrew, in towards the space at the tube’s centre. In the space of roughly sixty-four days, they will be transformed from round, nondescript cells to fully fledged sperm with heads
and tails; from being tucked away in inventory to positioning themselves in readiness for consumption – ejaculation.

If that ejaculation happens in the context of unprotected sex, it will only be possible for one out of the many millions of sperm to make it successfully into an egg. If one penetrates the egg,
the egg will harden to prevent another from entering. That is, if any succeed in entering at all. Achieving fertilization is a formidable task, and requires sperm that are fit for purpose. In the
process of making sperm from stem cells, many defects occur. Their heads may be too large or too small, tapering or shapeless. They may even have two heads instead of one. Some
sperm are made with bent tails, or tails that are too thin, too long, or too short, broken, coiled, or altogether missing. Some sperm have been found with a combination of defects.
Sperm with tail abnormalities will have little chance of swimming well enough to get anywhere near an egg. Those with head defects may be carrying damaged DNA, or an abnormal amount of DNA. They
may also be unable to use their head to penetrate an egg properly, even if they did get close enough.

The environment in which sperm are made may have a lot to do with how well they are formed, or the quality of their genetic material. Low levels of testosterone, and of the minerals zinc and
selenium, seem to be bad for sperm and male fertility. Lifestyle and other factors of biology can also affect the integrity of the genes carried by sperm: exposure to radiation, heat, cigarette
smoke, airborne pollutants, or chemotherapy drugs; sexually transmitted infections; ageing; a high body mass index; and medical conditions such as insulin-dependent diabetes – all can degrade
the quality of DNA.

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