The Big Question: Are scientists now really able to make sperm and egg cells in the lab?

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The Independent Online

Why are we asking this now?

Scientists in the United States led by Renee Reijo Pera of Stanford University School of Medicine have made primitive sperm and egg cells from stem cells taken from spare human embryos left over after IVF treatment. The emphasis is on "primitive" because they are not the fully-formed, mature sperm or eggs that are normally involved in conception. In scientific terms these cells are "germ cells", the immature cells that can, ultimately, give rise to sperm and eggs if they are allowed to develop further.

Why have they done this?

The aim is to understand the complicated biological processes behind the formation of human sperm and eggs. Eventually, it may be possible to use this information to make what are called "in vitro-derived gametes" or synthetic sperm and eggs.

This would be of great benefit to men and women who cannot produce their own gametes because it would allow them to become parents of their own biological children. But the basic scientific information gathered from this study would in any case further our understanding of how human sperm and eggs are formed, which would be very useful in terms of developing new treatments for both and male and female infertility.

What is the use of being able to make sperm and eggs from IVF embryos?

If it becomes possible to make sperm and eggs from spare IVF embryos it shows that the technique is a viable method of producing synthetic gametes in a test tube. However, ideally it would be important to do the same with cloned human embryos, derived from the skin cells of the person who is infertile. This will mean that infertile men could produce their own sperm, and infertile women could make their own eggs. It might even be possible for men to produce eggs and women to produce sperm, enabling same-sex couples to produce their own biological children with an equal genetic inheritance from each gay parent.

How far did the scientists get in making sperm and eggs?

The germ cells of both men and women start developing early in the life of a human embryo, long before adolescence and even birth. Dr Reijo Pera and her colleagues were able to identify the cells of the early IVF embryos that were destined to become these germ cells with the help of a green fluorescent marker gene that was only turned on in those embryonic cells earmarked for making sperm and eggs.

Dr Reijo Pera then tinkered with a number of known genes thought to be involved in germ-cell development and identified three, named DAZ, DAZL and BOULE, that are vital for a germ cell to mature into an egg or a sperm cell. She found that the DAZL gene was necessary to transform an embryonic stem cell into a germ cell, and the two other genes were important in the later developmental stages involving a type of cell division known as meiosis, which is critical for making sperm and eggs.

Dr Reijo Pera and her team managed to get quite a long way towards making mature sperm cells resulting from meiosis, but the egg cells were at a less-mature stage with incomplete meiotic cell division.

What is meiosis and why is it so important in the formation of sperm and eggs?

Normally, when cells divide into two, they keep the same number of chromosomes in each of the "daughter" cells. However, the unique feature of sperm and eggs is that the number of chromosomes are halved (to 23 in humans). This is important because when the male and female sex cells fuse together during conception, the chromosomes of the fertilised egg must revert to the normal number of chromosomes, which is 46 in humans.

In other words, meiosis is a type of cell division that allows the number of chromosomes of the "mother cell" to divide in half. So any attempt to make synthetic gametes in the laboratory has to stimulate meiotic cell division so that the resulting, synthetic sperm and the eggs each have only 23 chromosomes.

This is one of the reasons why making sperm and eggs from embryonic stem cells is so much more complicated than making the other specialised tissues of the body, such as heart muscle or brain cells, from embryonic stem cells.

What did the scientists say about their research?

"Our goal is to understand how you make eggs and sperm," said Dr Reijo Pera. "We know almost nothing about human reproductive development, and this gives us a new way to investigate it. The hope is some day to help those who are infertile. Ten to 15 per cent of couples are infertile. About half of these cases are due to an inability to make eggs or sperm, and yet deleting or increasing the expression of genes in the womb to understand why is both impossible and unethical.

"Figuring out the genetic 'recipe' needed to develop human germ cells in the laboratory will give us the tools we need to trace what's going wrong for those people."

What did other scientists say about the research?

One leading figure in the field, Darren Griffin, professor of genetics at the University of Kent, said: "This is a very elegant study. Although the [study] describes the transformation of stem cells into cells that are akin to gametes, it is important to note that the main significance of the work is not to attempt to generate gametes for couples who do not produce them naturally. Rather, the work describes a system in which various aspects of germ-cell development can be studied in a dish, rather than relying on animal models or removing bits of people's gonads."

Allan Pacey, lecturer in andrology at Sheffield University, said: "Ultimately, this may help us to find a cure for male infertility. Not necessarily by making sperm in the laboratory, which I personally think that is unlikely, but by identifying new targets for drugs or genes that may stimulate sperm production to occur naturally. This is a long way off, but it is a laudable dream."

So how far off are we from synthetic sperm and eggs, and what are the ethical implications?

Some commentators believe it is at least five years away. Other studies in mice have shown that it is possible to produce viable sperm, but synthetic eggs could be more of a problem. One study purporting to produce human sperm earlier this year had to be retracted because of editing errors in the scientific paper, although the scientists involved believe the science itself was sound.

As regards the ethics, the law in Britain currently bans the use of synthetic gametes in IVF treatment. But if they are shown to be safe, or at least as safe as naturally-produced sperm and eggs, there should be no overwhelming scientific objection to their use for treating male or female infertility. However, many people may not be happy with the idea allowing same-sex couples to use he technique in order have their own biological children.

Should we welcome the idea of making human sperm and eggs in a test tube?


* It offers the hope of children for both infertile men and women who cannot make their own gametes

* Even if scientists don't make eggs and sperm, our understanding of infertility will be advanced

* One day it might lead to same-sex couples having their own biological children


* This research is based on studies with human embryos and as such it is unethical

* It will lead to future develpments in this field that many will find unwelcome

* It is tinkering with nature and in any case the world is already suffering from human overpopulation