(10b) Embryology and society.

In this article I write about something amazing in life: developmental biology (more specifically about human development although most apply also to other animals and even plants) and how out of two tiny cells an organism arises with billions of cells. I mention also briefly about the effects of our knowledge on society: new applications such as IVF and stem cell research or even gene therapy to cure genetic diseases.

Science: embryology

The cell: introduction

Our bodies consist of two types of cells: reproductive cells or gametes and body cells or somatic cells. Somatic cells (e.g. liver cells, skin cells, nerve cells) are found all over our body except in the reproductive organs where in addition gametes are found: these are egg cells or ova (ovum = one egg cell) in the ovaries of women and sperm cells or spermatozoa in the testes (balls) of men .
1. Cell with nucleus and chromosomes that consists of DNA.


Eukaryotic cells (including human cells) consist of two main compartments: the cytosol and a nucleus within the cytosol (see fig. 1) (prokaryotic cells i.e. bacteria have only one main compartment). The main difference between somatic cells and gametes is within the nucleus: gametes contain 23 (n) chromosomes and are haploid while somatic cells contain 46 chromosomes and are diploid (= 2 x 23 chromosomes or 2n). A chromosome consists of a very long double DNA helix containing thousands of genes (more than twenty thousand genes can be found in the human body spread over all 23 chromosomes). Each plant or animal has its own number of chromosomes (e.g. body cells of cats contain 38 chromosomes while those of silkworm contain 56 chromosomes, thus the number of chromosomes is not a reference for the complexity of the organism).

The beginning of our lives

2. Gametes (ovum or spermatozoa) plus zygote.
During heterosexual sex, a man insert his penis in the vagina of a woman and via the penis the sperm cells enter the body of the woman. Sometimes the intercourse happens when a mature egg cell travels through the oviducts in the woman and after the spermatozoa reach the ovum, only one sperm cell can fuse with the ovum during fertilisation; the resulting cell is called a zygote (see fig. 2). As the zygote is the result of the fusion between two gametes, each containing 23 (n) chromosomes, the new cell has 46 chromosomes (2 x 23 or 2n) and thus becomes a body cell. The chromosomes in the gametes are almost similar, thus somatic cells contain each chromosome two times. The 23th chromosome is the exception because body cells of men contain one X-chromosome plus one short Y-chromosome while somatic cells in women have two X-chromosomes (fig. 3 shows the chromosomes isolated out somatic cells). The difference in chromosomes in somatic cells is due to spermatozoa which contain 22 chromosomes plus either one X-chromosome or one Y-chromosome while ovum contain also those 22 chromosomes plus always one X-chromosome. The Y-chromosome is important in the development of boys and thus sperm cells determine the sex of the child. Problem: Sometimes zygotes have incorrect numbers of chromosomes and most of these cells will not develop and die (spontaneous abortion) but there are exceptions. The best known are people born with Down syndrome where all body cells have one extra chromosome 21, thus the cells contain 47 chromosomes instead of 46.

3. 2 x 23 chromosomes in somatic cells.
After fertilisation, the zygote doubles its DNA to 92 chromosomes before dividing them over two cells, resulting in 46 chromosomes in each daughter cell (process called mitosis). This process continues and thus the number of cells increases (after each round of divisions there are twice as many cells if all cells survive). Each chromosome is DNA containing thousands of genes and each gene is found twice in body cells: one gene is found on chromosomes originating from the ovum while the other is on chromosomes originating from the spermatozoa. Somatic cells of men are an exception because they contain two different chromosomes 23 (i.e. X and Y)). Genes contain important information and cells translate the information into proteins. Each protein is a molecule with a specific function in the cells (e.g. collagen, haemoglobin). Before the cell divides, not only the number of chromosomes doubles, but also the amount of proteins increases before being divided over the two daughter cells. Problem: When a gene has an error (mutation) and thus the information is wrong, the protein is also incorrect what can result in malfunction of cells and either a baby is born with an illness (e.g mucoviscidosis) or is unable to survive.

Importance of genes and proteins in developing embryo 

The correct number of chromosomes and thus genes results in the formation of the correct amount of proteins in the fertilised cell. As a result the cell starts to divide, first into two cells, then four, eights, ... and finally becomes the species the cell is destined to become (in our case a human). Without going into too much detail (scientists only now begin to fully understand all these processes), the correct numbers of active and inactive genes in a cell are very important. When the number of copies of DNA (e.g. in an unfertilised egg) is too low, not enough proteins are made and the cell will not divide (cell also didn't end the meiose (due too incorrect amount of proteins??)) and only after fertilisation the cell will divide.

But, it is more complicated because not always are both genes active and produce proteins. This results in the correct amount of proteins (an incorrect amount of proteins results in miscarriages). In other words, some genes are active on both male and female DNA and thus both genes contribute to the amount of proteins produced while other genes are only active on either the male or the female DNA while the second gene is inactive resulting in less proteins then when both genes would be active. This results in the correct balance of proteins after the fusion of a sperm cell with an egg cell. For instance, when a body cell needs only a moderate amount of a certain protein then this is possible because in e.g. sperm cells the gene is not active while in ova the gene is active. Thus, after fertilisation, the zygote contains only one active gene resulting in a moderate amount of protein in the cell. This suggest that embryos originating from two ova have (in my example) two active genes and produce too much protein while those from two sperm cells have two inactive genes and have no protein at all; in both cases the cell is not viable. Therefore, we can conclude that fertilisation is only successful between an ovum and a spermatozoa. This can also explain why sometimes, even when one gene has a mutation, the person is not ill: if the cell only needs one active gene then the correct gene makes enough correct protein. However, when both genes are necessary to produce enough proteins and one gene has a mutation then the person will be ill.

Whether a gene is active or not depends upon certain molecules attached to the gene and this is studied in epigenetics, a new field in science.  Epigenetics may one day explain why e.g. embryos of nonsmokers develop faster than those of smokers, even when both embryos have correct DNA (i.e. no mutations): the translation of genes into proteins not only depends upon a correct DNA sequence but also on the molecules attached to the gene and these determine how easily the gene can be translated and thus its activity. The attachment of these molecules to the DNA may change when the mother smokes and these changes can pass down a few generations. Another example: scientists search for a gay gene but maybe that gene does not exist and can the existence of homosexuality be explained by changes in the molecules attached to the gene. It is a very interesting new field in science.


4. Morula
Thus, proteins are made in the fertilised cell but after several divisions of the cell, slightly different amounts of protein exists between the different cells as the proteins are not divided perfectly equal over the two daughter cells. The minor imbalances in protein levels between individual cells become sufficiently big after a few divisions, forcing cells to develop in one or another cell type. E.g. after about four divisions (the zygote has 16-32 cells and is called morula (see fig. 4), some cells will form the embryo while other cells will form the placenta and now the morula is able to implant in the uterus. The process of imbalances continues and results in different cell types. E.g. some cells produce slightly more proneural proteins and become nerve cells while other cells produce factors that force them to become liver cells. The development in one or another cell type is further strengthened by neighbouring cells influencing each other. E.g. cells that develop into neurons prevent surrounding cells to become neurons but stimulate them to become supporting cells, resulting in a correct balance between neuronal and non-neuronal cells. Finally, cells in one part of the body influence the development of cells in other parts (this continues throughout our whole life by means of hormones or nerve cells). Ones a cell differentiates into a certain cell type, the cell start to produce proteins specific for that cell type and can no longer become another cell type.

Further development

5. Embryonic development of animals
After fertilisation, we are not yet a human (as some people claim): first we are one cell, then a clump of cells with the ability to develop in all the different cell types present in a human body, depending upon growth factors and their place in the embryo. These early cells are called embryonic stem cells because they can develop in any cell type of the body while the final cells (e.g. nerve cell or liver cell) are called differentiated cells that are unable to change. The central nervous system starts to develop at the beginning of the third week and at the end of the third week the human embryo is not much more than a tube of cells and looks like the embryos of fish or other animals (upper row of images in Fig. 5). Only after day 28, arms start to develop and although the human embryo now looks different from that of a fish, it still looks similar to that of a chicken or rabbit (second row in Fig. 5). Only after about one and a half month, we start to see a human form (third row). But even then, many parts of the body are still developing and a spontaneous abortion can still occur when things go wrong during the development. Thus, nature often ends pregnancies when the development of the embryo or foetus goes wrong. Therefore when doctors notice something is seriously wrong with the developing baby (e.g. heart defect), an abortion can be considered to prevent a wrongly developing baby being born who may suffer badly during life or even die by birth. Although, techniques are developing so quickly that some defects (e.g. spina bifida) can now be treated while the foetus is still inside the womb.

Importance for society

Stem cell research

Since many years there are discussions regarding the use of embryonic stem cells in research. Embryonic stem cell research should not cause a problem because, although the cells originate from humans, they are not yet a person as not even an nervous system is formed and thus the embryo can't interpret information. Indeed, the cells of an embryo used for research are simply a "clump of cells". Moreover, embryonic stem cells can only be used within a short period after fertilisation before they differentiate and start to behave like adult cells. Furthermore, under the right conditions the stem cells are able to divide for many years without developing into an embryo; as a result the cells can be used for many years and thus not many embryos are needed to obtain these cells for research. Finally, often scientists force the embryonic stem cells to develop into certain cell types (e.g. heart cells) so scientists are able to study the involvement of genes in the embryonic development and why things can go wrong. Because these stem cells become differentiated cells, they no longer have the capacity to become a person and after the research, the cells are destroyed. Scientists also try to use embryonic stem cells for therapies although there are safety concerns. Older embryos are only studied after (spontaneous) abortions.

But we enter a time when embryonic stem cells are no longer needed. Only a few years ago, scientists discovered adult stem cells (i.e. undifferentiated cells present throughout our body and still able to divide and develop (differentiate) in many cell types, e.g. bone marrow (blood) stem cells can develop into the different types of blood cells). Scientists not only use these cells in research but also try to use them to cure illnesses with the added advantage that these adult stem cells, taken from the body of a patient, will not be rejected by the patient when returned. In a few countries such as France and England, some "bubble boys" (boys with a malfunctioning immune system due to an incorrect gene on the X-chromosome (X-SCID)), were cured using gene therapy (see Fig. 7 for principle of gene therapy) whereby the incorrect gene in bone marrow stem cells was replaced (with the help of viruses) with the correct gene. Unfortunately, as a consequence some children developed leukaemia and some died (thus the method needs improvement).

Even more exciting is the discovery that differentiated cells can de-differentiate, (i.e. revert) to stem cells (called induced pluripotent stem cells (iPSC)) when only three or four pluripotency genes are inserted in adult somatic cells. After insertion of these genes into a differentiated cell (e.g. skin cell), the cell becomes a stem cell. The advantage is that easily accessible cells can be used to make stem cells.

The latter two kind of stem cells have the advantage that no embryos are used and thus are ethically more acceptable. These stem cells are used to investigate illnesses and to find cures. But it all started with embryonic stem cells because we had to understand the definition of a stem cell before we could find or design other stem cells. What an exciting time.

IVF and design babies 

6. Two methods of IVF.
As we start to understand the processes of our development, we can use them for all good reasons. One of the best known is the possibility for infertile parents to have children after artificial insemination or in vitro fertilisation (IVF). Many people today know people who became parents thanks to this method while in a not very distant past they would remain childless. Remember, the first person born this way was in July 1978, only 34 years ago and her parents were happy the new technique gave them a child. Another advantage of IVF is that embryos made in a lab can be screened for the presence of genetic diseases in families with a history of the illness and only healthy embryos are implanted in the womb. The other embryos can be used in research to understand the mechanisms of the disease and find a cure (mutations can always occur and thus people can always be born with the illness). This technique will result in the disappearance of the disease in the family as only healthy embryos are returned.

However, I believe we should never select people on the basis of their gender. Indeed, most humans on this planet have the unnatural habit of preferring boys over girls, especially a macho boy. But, in societies where only two people (man and woman) can marry while in some societies one man can have many wives, the society needs at least equal amounts of boys and girls (certainly when homosexuality is forbidden). Today there are countries with many more boys than girls (e.g. China and India (also due to abortion of girls)) while in many societies men only earn respect when they marry a girl and have children. In these societies, men (often machos) may have to fight (and kill) each other for girls, after which the natural balance is restored when enough men are killed, although often afterwards the girls outnumber the men. A solution could be that when there are too many men, homosexuality is allowed so straight men can have the girls (although there will also be lesbians who don't want the men). I think the natural order is more girls are needed than boys: one man can produce offspring with many girls in a short period while a woman can satisfy hundreds of lovers, she can only produce offspring from one man and only about every nine months, thus men may still fight for their right to have a child and they may even kill the child of another man (normal animal behaviour).

7. Gene therapy, whereby a virus is used to insert a correct gene.
As mentioned above, gene therapy may become one of many cures to threat illnesses whereby viruses introduce the correct gene into cells of a person to replace a damaged gene, allowing the cells to produce the correct protein (see Fig. 7). Many people fear (or hope) one day this technique can be used to design babies according to the wishes of the parents. This is a positive development when used as a cure against genetic disorders (see above X-SCID). However, I think it will not be wise to design children (if possible) according to the wishes of parents. Imagine, parents want the best for their child and pay to insert genes that will make their child good in languages and maths. But, someone else has more money and uses more genes so that child may be better, or at least that is what the child will blame its parents if it is less successful than the other child. Or the child loves dancing but is not very good, then it can blame its parents for selecting the wrong genes. Or what was considered valuable during the making of the baby is worthless when the child is an adult (in the past macho boys didn't dance while now good dancers are very respected). Thus, whenever a child is not the best in something, it can blame its parents, even when the child is not good because of laziness. Remember, there can only be one boss and thus the others can blame their parents they didn't spend enough to make them better. Or, the gene is inserted at the wrong place and as a result the child is disabled, having every reason to blame its parents. Thus, I think we should allow the random factor of nature so different kinds of people are born and only use gene therapy to cure people. Because, if every child is designed, maybe the person who has no genes inserted will be considered so special and spontaneous that that person is the most wanted. 

Religion

Abortion and embryonic stem cell research should not be seen as killing humans as no human is yet formed. However, people should not need to use abortion as a way of birth control (the religious right agrees) when contraception (e.g. condoms or contraceptive pill) can be used (the religious right doesn't agree) while abortion should be considered when the foetus has severe problems and then the abortion should be carried out as soon as possible (the religious right certainly doesn't like this). The latter also means abortion should not be used to remove an embryo because one thinks it may become a person one does not like (e.g. male versus female, gay versus straight if it was possible to know before birth). Embryonic stem cells research should be allowed (the religious right doesn't agree) because embryonic cells in the earliest stages of the pregnancy are used when no person is formed yet and these cells can be used for a long period reducing the number of embryos used. But more importantly, today scientists are able to take adult stem cells from children and adults or even more interesting, scientists can revert differentiated somatic cells (e.g. from skin cells) in stem cells and thus there will be less (no?) need anymore to use embryonic stem cells (and the religious right should be happy now but still they object).

Many (not all) ordinary religious people say they oppose stem cell research, but (as the cartoons shows) in reality many are hypocrites, as in silence they hope scientists will find cures for all kind of illnesses (the same hypocrisy towards contraception). The hypocrisy has severe consequences for society because politicians feel obliged to slowdown progress in research and thus in finding cures (or GM food) even when scientific data demonstrate their safety. Furthermore, some politicians join the "spiritual leaders" because they hope it will boosts their career when they have the (financial) support of religious organisations (many churches are extremely rich). For instance, can you imagine what will happen in the USA when many Tea Party members are elected for Congress and when Republicans (and some Democrats) continue to bow for their demands to gain the vote of the right? End of abortion? End of contraception? End of stem cell research? It is possible. And as the USA is powerful, they may force other countries to do the same. Indeed, those hoping for a cure will have to wait much longer. The journal New Scientist (October 29 2011) published interesting articles entitled "Unscientific America" about the retreat from reason and its dangers. However, lots of the concerns from ordinary people find their origins in ignorance. Therefore, people can be religious but should not only listen to people preaching against science because they are protecting their own job and wealth, but they should try to understand what scientists are doing before condemning the research and only then should people form their own opinion. But a major problem is that many people refuse to listen when scientists try to explain their research because they think scientists try to influence them.

People should raise their concerns about new techniques so scientists will not take them for granted but try to find better ways to solve problems (i.e. embryonic stem cells may be replaced by adult stem cells or iPSC, reducing problems such as rejection of foreign tissue). But people should be willing to listen to scientists so they can be educated and understand the benefits of research. Documentaries are ideal to explain science. Scientist should also make it clear they do research not only for the honour (also important) but mainly to improve society. People should understand the benefits of research (even when not immediately visible). But equally, scientists shouldn't make fools of religious people as this will radicalise them (and religious people are still a (dangerous) majority) unless scientists can prove with certainty Gods do not exist; indeed some scientists are as dogmatic as religious people by claiming something without scientific proof (although this should not stop them arguing based upon reason).

Nevertheless, there will always be people who never ever want to listen to reason. They will never ever accept scientists try to improve the lives of people. There will always be people who think they are the only one who are morally right and they are prepared to kill others to proof that. And do ordinary people sometimes need diseases before they accept the benefits of science? E.g. vaccines saved many people from deadly illnesses but today some people question their safety and do this in a loud voice so everyone will hear them. But during epidemics (such as in France in 2011 when there was an outbreak of measles affecting thousands of children), then the children can't get their vaccination quickly enough while the people claim the politicians, doctors and scientists failed them.

In conclusion:

It is fascinating to know that two microscopically small cells are the origin of a whole human (or e.g. a whale) and although many things can go wrong, in general healthy babies are born. It is also exciting how we, via our knowledge, are becoming able to cure illnesses that were deathly in the past. When in the future most (maybe all?) diseases may no longer cause serious health problems or even kill due to the continued improvements in medicines and the use of gene therapy and stem cells, then the numbers of people will no longer be controlled by nature (nature kills easier when too many people live in a small area because diseases spread faster), and thus we can't continue behaving like animals, producing off-spring each time "we did it" (= had sex). Then birth control via contraceptions will be a necessity. Another advantage of birth control is that we no longer need wars to reduce our numbers when we become too crowded and in need of more living space to house and feed everyone. Of course, we will aways die, sometimes because of accidents but certainly because of old age because each cell in our body has a time limit and replacing all cells with new ones would be impossible. By the way, who wants to live forever and work millions of years and see each day the same things? In addition, the newborn babies need their space, otherwise we kill each other in war.

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