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Progress in medicine is driven by imagination, research, innovation and courage. In the last 20 years, reproductive medicine has depended on scientists, doctors and nurses demonstrating these qualities -- an interdependency that continues. This web page looks at the developments in reproductive medicine being actively researched today and examines what the technological keys may be to creating, amplifying, preserving or restoring a woman's control over her reproduction when there's infertility or miscarriages, and when, for more personal, family-orientated reasons, technological help in having a child is asked for. I discuss: Oocyte Competence and Cytoplasmic RepairReturn to Top There are still many reasons embryos don't do as well as we would like in the IVF lab and, after embryo transfer, in a woman's body. In many cases there can be an inherent embryopathy present, acquired from the sperm or, more often, from the egg before fertilization. In some cases this embryopathy will be chromosomal. In many cases we suspect that it might be wear and tear of the egg's, and hence the embryo's, mitochondria. In vitro culture conditions can make a critical difference for these embryos (discussed on WebPage 20), but the shortcomings of such eggs are still poorly understood. The oopauseReturn to Top Human females, whose ovaries at birth contain all the eggs they will ever develop, usually lose the ability to get pregnant in their late 30s or early 40s, about a decade before the menopause, when the ovaries' eggs are more or less finally depleted. This normal sterility has now unequivocally been linked to a decline in the capacity of eggs from older women to develop, after fertilization, into viable embryos, and almost certainly this is in turn due to a defect in the oocyte cytoplasm of the remaining eggs. At Sydney IVF we call this phenomenon the oopause. In modern societies the reality of the oopause sits increasingly awkwardly with the longstanding, steady social development of a rising age at first childbirth, which is leaving women who wish first to pursue a career with ever shorter time in which to have children, an opportunity many inadvertently and lamentably miss. Cytoplasmic transferReturn to Top A team of researchers in New Jersey led by Dr Jacques Cohen have demonstrated that there is a small group of older women (late 30s, early 40s) who still have apparently adequate numbers of eggs, but who have consistently poor embryos. Dr Cohen showed that if a relatively small amount of cytoplasm is taken from apparently healthy donated eggs, and injected into the older eggs at the time of fertilization by ICSI, these people's embryos look and do much better. The chance of pregnancy increases significantly. Dr Cohen's team has also demonstrated, in some of the children of the women, that mitochondrial DNA from the donor forms part of the inherited complement of mtDNA in the cells of the offspring. Critics have called this "germ line gene therapy", but I disagree (see the box, Possible hazards with cytoplasmic transfer). It is not known whether the ooplasmic defect in the eggs of older women lies in a quantitative or qualitative deficiency in oocyte mitochondria or whether older eggs are missing a critical factor in the cytoplasm, such as an enzyme or an RNA molecule. There are typically 400,000 or more mitochondria in a human egg at fertilization. Our work at Sydney IVF reveals a range of mtDNA copy number between 100,000 and 5 million. The small amount of cytoplasm shown to be beneficial, namely 5-15% of the egg's volume, points to a benefit more likely to be based on the addition of a missing catalyst rather than on the bulk addition of a missing volume-dependent material such as functioning mitochondria (akin, say, to replacing blood by transfusion in a person with anemia). Where does its future lie? The technique is promising. If only we knew how it worked, we might know what side effects to look for. The children born have been clinically normal; the oldest is four. Knowing the difficulties you can expect as you get older, the thought will occur that maybe you can store some eggs when you are young, to make use of after a later birthday. Usefully Conserving Young EggsReturn to Top There are two steps, neither of which has been perfected yet. Safely freezing unfertilized eggs As it was in the first edition of this book, the holy grail in the field of preserving female reproductive potential is to reliably preserve eggs, first, without having to stimulate follicles to the point of ovulation, and second, without having to fertilize the recovered eggs with sperm before storage. This remains a woman's present only hope for leaving having children until a later stage of her career or personal development, a time after her biological clock might have taken her past the oopause. Women about to receive potetially sterilizing chemotherapy for cancer or for serious immune diseases have a similar, even more urgent imperative. The present emphasis for research is on freezing eggs well before ovulation -- well before they acquire the delicate structure and machinery that enables them to receive a sperm cell and complete the process of fertilization (for a technical explanation of the difficulties, see the WebPage 21 box, Poised to spring). Resting eggs, in resting primordial follicles, may be the most stable of all to freeze. Many IVF programs are freezing "slices" of ovaries -- obtained by biopsy at laparoscopy (and usually packed with primordial follicles) -- for just this reason. But it's one matter to freeze the tissues, store them and thaw them. This we can do. But there has been little or no success so far in bringing the thawed, still-immature eggs to the point of full development at which they can be fertilized. There are two ways we might try it: developing the follicle and its egg in the laboratory, which is called in vitro maturation; or simply transplanting the stored ovarian tissue with its primordial follicles intact back into the body (which is how it was originally done in sheep). Developing eggs from immature tertiary follicles Take any egg out of its ovarian environment, separate it from its follicle cells, and it will mature spontaneously. It will complete the first division of meiosis and, theoretically at least, be ready to be fertilized. Researchers at Monash IVF, in Melbourne, have secured such fertilization using IVF techniques on eggs removed from antral follicles down to just a few millimeters in size. A number of women have conceived and had babies from eggs obtained this way. But unlike the same procedure in cows -- in which veterinary surgeons get pregnancy rates of over 60 percent using IVF with eggs from small tertiary follicles -- the chance of women getting pregnant this way is still less than 2 percent. The smaller the follicle, the less likely it is that the egg will mature normally -- and the more we have to learn about what's needed to get it to a normal, fertilizable stage. Much more work needs to be done before such human in vitro maturation from tertiary follicles becomes reliable, but the project is worthwhile not just for reproductive insurance; it would also be good not to have to stimulate the ovaries for superovulation in assisted conception programs. Meanwhile even more work is needed before eggs from primordial follicles will be able to be used reliably after in vitro maturation. Remember this is a process that nature takes 8 months to achieve within the ovary -- see WebPage 3). So far a normal embryo, with a successful birth, has been achieved in just one mouse. Dr John Eppig and Dr Marilyn O'Brien, who research mouse eggs at the Jackson Laboratory, Bar Harbor, Maine, obtained this one normal pregnancy (and another which miscarried) after transferring 190 two-cell embryos to the fallopian tubes of properly prepared mice. This is so far a rather discouraging result, given that conditions in mice can be much better standardized than they can be for women in clinical practice. A better option for primordial follicles after storage seems to be to transplant them straight back into the tissue of the animal or person they came from -- and to allow nature to develop the follicles, but so far that too has not been successful in humans (for more, see the box, Saving your ovary for later). Sex and Genetic Trait SelectionReturn to Top As The Economist, a London-based weekly newspaper, has said, "People are generally free to choose how to bring up their children. If they want to choose their child's sex as well, why not?". The same could be said about choosing whether or not to try and suppress a familial trait considered harmful or distressing. And, in both cases, it is not as if people haven't tried. For centuries, women and their husbands have visited witch doctors, astrologers and charlatans aiming to control that quintessential matter of chance: whether the next baby will be a boy or a girl. And they have gone to church or other place of worship and prayed, hoping for a modicum of intervention from the almighty. What's new is that we are, today, starting to use reproductive technologies that make these choices substantially more effective. I discuss here the present state of the technology that's needed to control sex and to screen embryos for genetic traits. Let me say at the outset that I do not agree that this means we are designing babies. "Designer babies" is a cliche that invokes thoughts of a blank canvas ... one we start pasting genes on ... any genes. "We'll take a pair of these rare genes for green eyes; let's go heterozygous for freckles; the newly discovered allele for dimples would be a cute touch ...!" This is a long, long way from reality. Reality used to be that a couple had maybe 10 children, among whom there would be a wide assortment of genes ... but only, of course, their genes, genes the couple between the two of them already had. That much is the same today. It's not a blank canvas. But today not many couples are going to have 10 children. They might only want one. And irrespective of how many children they've had, what's wrong with choosing the next child's sex ... or making sure that some physical characteristic that Sam has always detested about himself or herself, does not also trouble one or other of their children? It might sound trivial to someone else, but if it's not trivial to Sam and Sam -- and if they're not asking someone else to pay for it -- why can't they have their IVF embryos checked for it (assuming the gene can be identified) and then just transfer an embryo or embryos without it? There are two important points to remember about the biology here. First, no gene (unless both parents have it) is going to appear in more than, on average, half the embryos. And we're at least a generation away from even thinking of trying to repair a gene. It will always be easier to test for it (and to not use an embryo with it) than it will ever be to alter it. Second, how the different genes (all 32,000 or more of them) assort with each other is totally out of our hands, even in an IVF lab. In a restricted number of embryos, as is always the case after egg retrieval and IVF, probably much less than half will even be normal (in terms of having the normal number of chromosomes); of these, on average no more than half will have one wanted gene, no more than a quarter will have two wanted ones, an eighth will have three ... and so on. If you want to get too picky, you quickly run out of embryos. And a third point -- a social one. We see on WebPage 22 the extraordinary extent to which, especially in the U.S., babies are being born using sperm and/or eggs from anonymous donors, where fully half (sometimes all) the genes in a baby are from a total stranger! It's not illegal yet. (Some countries are starting to legislate that children must be able to track down their genetic parent or parents, the way the law is increasingly recognizing the rights of adopted children.) What, in this big picture, is the big deal about selecting one or two genes from within your family for your child? If this is "playing God", then what God has been playing is dice. Maybe He or She is having some time off relaxing with some trivial decision making … at the very least, if you are into metaphysical power, the heavenly drama of whether Ms Jones in Ermington has a boy or a girl next time, or deciding which of her 300,000 eggs it will be that will become little Jeannie or Johnnie, will have been delegated for decision-making to a lesser immortal. From hocus-pocus to sperm-cell sortingReturn to Top Since the discovery that the X-chromosome is bigger than the Y-chromosome, scientists and others have tried to exploit the difference by aiming to separate the supposedly heavier X-bearing sperm (destined to form girls) from the supposedly lighter Y-bearing sperm (destined to form boys). To begin with, Y-bearing sperm have long been thought to swim faster -- and so to get to the egg sooner. If you then conduct a race - by abstaining from sex until the egg has been ovulated ("late sex") -- you should increase the chance of having a boy. On the other hand, if you want a girl, this theory has it that you should have sex well before ovulation, let the Y-bearing sports jobs run out of puff, and the chances are that the slow but steady X-bearing sperm will be fittest by the time the egg appears in the fallopian tube ("early sex"). Landrum Shettles, a gynecologist from Alabama, popularized this principle in the 1970s, adding to the recipe a mildly alkaline vaginal douche (made by dissolving 5 grams of baking soda in half a liter of water) before intercourse for boy-selection, or adding a mildly acidic douche (20 mL of white vinegar in half a liter of water) before intercourse for girl-selection. Some fantastic results have been claimed for Shettles's method. For example, Dr Cedric Vear, a family physician from rural New South Wales, reported in The Medical Journal of Australia (MJA) in 1977 a perfect outcome among ten consecutive couples. For some reason he stressed the need to avoid frivolity, to, as he put it, "(impress) on both parties that the procedure is a scientific exercise and not an emotional or erotic skirmish"! What a kill-joy. What would Vear have thought of trying for a boy by holding off having sex till there's a full moon shining through the window then timing a climax to coincide with the crow of a rooster watching from the end of the bed? To be sure, Shettles advised avoiding orgasm for conceiving a girl. But I can't work out the logic. Using the Shettles methods, and publishing in the MJA in 1985, Dr Barbara Simcock refuted Vear (and Shettles). Among 73 women the success rate for choosing daughters was 50 percent; for choosing boys, she concluded that "the use of [a] modified Shettles' method appeared to decrease the delivery of a male child". More recently, attention has been focussed on trying to separate X-bearing sperm from Y-bearing sperm in the lab, prior to assisted insemination. Most popular of the procedures has been passing the sperm cells through a column made up of the human protein albumin, which was first reported in the distinguished British journal Nature in 1973, by R.H. Ericsson and others. Dr Ericsson has since been associated with a number of clinics in the US, Asia and Britain, at which it's claimed that if couples use their albumin-based sperm cell separation techniques they will conceive a child of the desired sex with more than the normal approximately 50 percent probability. Ericsson's method, as published in 1973, reportedly produced a concentration of Y-bearing sperm. A number of investigators have explored this claim by testing the sperm obtained with a fluorescent dye that stains part of the Y-chromosome (using a reliable technique called fluorescent in situ hybridization, or FISH). Using FISH, investigators in laboratories from South Australia to Barcelona, Spain, have been unable to show significant enrichment for Y-bearing or for X-bearing sperm using albumin separation columns. So the effectiveness of sex selection clinics based on Ericsson's sperm selection method has to be questioned. What we have learned from them, however, is how many people are after boys and how many are after girls (see the box, Should feminists be worried by sex selection?). MicroSortReturn to Top In 1990, patents were granted to the US Government for the technique of sperm-cell sorting to concentrate X-bearing and Y-bearing sperm by using a separation technique based on these cells' different DNA content, and using a technology called flow cytometric sorting. Cell sorters based on flow cytometry are in wide usage in medicine. Blood transfusion services, for example, use them to separate the different cells in donated human blood for specific transfusions of red cells (for anemia), white cells (for infections) or platelets (for bleeding). Dr Larry Johnson, working at the US Department of Agriculture laboratories in Beltsville, Maryland, successfully adapted cell sorters to deal with the unusual flat shape that sperm cell heads have. He stains the cells with a special, non-toxic dye called a fluorochrome, which emits light when excited by ultraviolet light from a laser. A sperm cell passing through the sorter is shot by the laser; if a detector at right angles confirms that the sperm's flat surface is actually facing the laser then a detector in line with the laser 'reads' the intensity of light radiation emitted. The sorter can be set to look for the slightly smaller amount of light a Y-bearing sperm emits or the slightly greater amount of light an X-bearing sperm emits. Either way, each sperm cell passing the test is then pushed electronically into a separate path that leaves the cell sorter, for collection and later use. Dr Johnson has used the fluorochrome-based cell sorting method with sperm from a number of species, including rabbits, cattle and pigs. As well as testing the resulting Y- or X-enriched sperm populations with FISH, the sex of offspring produced from inseminating the animals with these 'sperm fractions' has been studied. Proportions of females ranged from 75 percent in pigs to 94 percent in rabbits when the cell sorter was set for enriching X-bearing sperm. Proportions of males, when the cell sorter was set for enriching Y-bearing sperm, ranged from 70 percent in pigs to 86 percent in rabbits. Dr Ed Fugger and Dr Joseph Schulman, working at the Genetics & IVF Institute in Fairfax, Virginia, outside Washington DC, have successfully applied Dr Johnson's method to human sperm (www.givf.com). Writing in the journal Human Reproduction in 1993, Johnson, Fugger, Schulman and others reported an average of 82 percent X-bearing sperm and 75 percent Y-bearing sperm, depending on which type of sperm the machine was set to sort for. Dr Schulman then went on to report the achievement of a human pregnancies of the wanted female sex for most couples who trying for a girl for family reasons or to avoid the risk of a genetic disease in their child such as hemophilia (the gene for which being a recessive one found on the X-chromosome, the second of which in girls will usually be normal and thus stop expression of the disease). Because of the rather slow nature of the cell-sorting process (each sperm has to be electronically tested, one at a time, and then shunted to one side or the other), the technology I believe is better suited for IVF with ICSI than for IUI, although it will depend on the relative cost of these procedures. No doubt further developments of the technique at the Genetics & IVF Institute will improve its efficiency. By the mid-1990s, we for the first time had a technology for changing the chance of a wanted girl from one in two to four in five, and for changing the chance of a wanted boy from one in two to two in three or better -- but at a formidable price in dollars and with odds that fall well short of certainty. To get better odds than this we move to IVF with PGD. Preimplantation Genetic DiagnosisReturn to Top Before cell-sorting technology was available to improve the chance of achieving female embryos, several British families at high risk of having children with hemophilia used IVF and biopsy of resultant embryos to work out which were male and which were female. The rationale was (and is still) that genetic diseases inherited by sex-linked recessive inheritance will manifest in boys but not in girls. The reason is that, being recessive, the abnormal gene will not be expressed (and therefore will not cause the disease) if there's a normal second gene (or allele) present among the chromosomes. For such genes on the X-chromosome, one allele or gene is enough: the Y-chromosome is too small to carry a complementary savior gene. As well as hemophilia these sex-linked genetic diseases include Duchenne's muscular dystrophy (a progressive weakness of the muscles) and Tay Sach's disease (a serious brain disorder). By using the polymerase chain reaction (PCR) to amplify pieces of DNA known to be unique to the Y-chromosome, researchers led by Dr Alan Handyside at London's Hammersmith Hospital were able by the early 1990s to distinguish male from female embryos, and to transfer just those that were female. (The alternative for these families would have been to wait until pregnancy was established and then use either high-resolution transvaginal ultrasound or conventional karyotyping of cells obtained by chorionic villus sampling (CVS) or amniocentesis to discover the sex of the fetus, aborting it if a male.) A number of IVF centers now have the capability of performing preimplantation genetic diagnosis. Figure 20.3 shows such micromanipulation underway at Sydney IVF. For chromosomal diagnoses, such as determining sex or discovering trisomies (including Down's syndrome, or trisomy 21, and Klinefelter's syndrome, which is 47,XXY) and monosomies (such as Turner's syndrome, 45,X), FISH can be used. For molecular diagnosis of specific abnormal genes, such as the gene for cystic fibrosis, PCR is the only method possible. Although it's not likely that more than a tiny proportion of IVF eggs or embryos will be subjected to biopsy for PGD at any time soon, for families affected by serious genetic diseases who have other reason for considering IVF, this ability to make diagnoses before embryos are transferred is an important development. Whether less serious genetic impairments will lead to such extreme technological intervention only time will tell. And, recently, families anyway planning a further child in circumstances where an earlier child is terribly sick with, typically, a blood disease for which a bone marrow transplant has been advised, have considered IVF with PGD to ensure that the newborn baby's cord blood (from which bone marrow stem cells can be isolated) will match that of the older sibling. Critics describe these as slippery slopes into designer embryos. Well, if there is a slope, I think it's got hills as well as dales and is not particularly slippery: as genetic knowledge and methods for diagnosis and possible treatment slowly accumulate, societies will have more time to debate these issues than prophets of Utopian doom would have us believe. Couples have always had children for mixed reasons and the love they end up showing for their children might or might not have been what was on their separate minds when conception occurred. The important issues are not knew for experienced medical professionals. We are not obliged to assist when it is plain that a planned pregnancy is evidently and solely a means to someone else's end. Most requests for our help, be it prevention of transmission of genetic disease, help achieving a balance of genders in the family, or raising a new child who at birth unwittingly saves the life of an older sibling, arouse nothing but compassion. For sure, though, as sperm-cell sorting, ICSI and PGD raise the value of individual embryos, not only will our expectations of (and our identification with) a single embryo grow, we will want to be surer than we can be yet that an apparently normal embryo that's transferred will in fact implant to form an embryo, a fetus and then a baby. That means two things. First, we need to be sure that all the chromosomes are normal, not only the 5 or so we can test with the restricted number of fluorescent dyes available for FISH. The most promising technique is described in the box, Comparative genomic hybridization. Second, once we've established that the egg's chromosomes are normal (see the box, ... and polar body analysis) we need to be able to test the cytoplasm of the egg to check its metabolic status, to make sure it has the power it needs to propel itself into a normal implantation and gestation. If an otherwise normal egg's cytoplasmic metabolism is not up to speed, Dr Cohen's work with cytoplasmic transfer described above suggests it might be possible to repair it. Hope, Hype and CloningReturn to Top Transplant surgeons and their support staff today have the technical ability to graft a donated uterus to a man. Why don't they do it? The world's first male pregnancy could follow! Not sexy enough? Or is it too obviously freaky to risk a good professional reputation on? Cloning is more mysterious. It seems more attractive. I'll be explicit. There's probably no better medical purpose in cloning a human individual than there is for a man to bear a baby. (And the reason, such as it is, is that "surely everyone should have the chance of having his or her own child"!) Not everything in medicine that can be done, is done. In practice there has to be a good reason to go to the trouble and expense, especially when a team of skilled people needs to be assembled for the task. The trouble with cloning is, first, the hype that clings to it. The hype is now such that, like unthinking moths to a flame, the limelight of fame beckons a class of doctor and scientist whose work might otherwise attract little attention or respect. More understandable is the desperation of infertile couples or childless people who are beside themselves with hope. The second problem with cloning is that you need to understand a lot of biology to appreciate why cloning is never the answer to infertility. "Cloning" entered the language in 1903, since which time the OED refers to it as reproduction by "budding", splitting off part of what we now know is a diploid, multi-celled organism to form another. The word was first used in botany, in relation to plants … that is, replicating a plant by taking a cutting. The word diploid is part of the key: it means two of each chromosome in each cell's nucleus. In other words, higher plants and animals carry, in every cell other than the sex cells (the gametes), one of each of their two parents' chromosomes. In contrast, a sperm cell or an egg cell has half this number (they are haploid), so that with fertilization the diploid state is reached again and the unique new organism as an embryo has the double DNA code it needs to develop securely, generally masking the few genetic imperfections we all carry on one or other chromosome. This process is called sexual reproduction. Forget whether the organisms had sex or not. IVF, or in vitro fertilization, to a biologist is unequivocally sexual reproduction -- even without the sex. Cloning, which involves no sperm, and uses an egg to put a budding nucleus into it, equivalent to taking a cutting, is asexual reproduction, just as practised by amoebas, yeasts and hopeful horticulturalists. Writing in the influential U.S. journal Science in June 2000, Canberra cell biologist Robert Blanden and a colleague, Edward Steele, stated
In other words, it was for good reason that, a billion years ago, nature took the expensive step of doubling up on the chromosomes, just so that they could swap bits of themselves around, randomly recombining, before competing as eggs (and less probably as sperm) for the privilege of passing to the next generation. While the eggs await this chance for life in the next generation, the female body protects them from too much metabolism and cell division. That's why all the eggs are formed as a fetus and then rest in the ovaries as primordial follicles (see WebPage 3). Not so for the body's other cells. Hell-for-leather they divide, their DNA mutates and wears out, and some cells mutate enough to become cancers. And these are the cells the cloning doctors are trying to propagate as new people. If cloning is a bit of a circus trick -- remembering though that most circus tricks go right more regularly than cloning yields a healthy-enough offspring -- where does the hype fall short of the hopes of the infertile? The bounds of what IVF can achieve for the infertile lies, first, with sperm. Here huge inroads have been made with ICSI: if there are even a few living sperm extractable from the depths of a testicle, healthy children can follow, as we see on WebPages 10 and 20. It's aging eggs -- eggs from older women -- that spell the practical limit to IVF treatment today, as we discussed above. Cloning does not avoid the need for eggs, so it's no substitute for tired eggs. It's no cure for the oopause. Is cloning a substitute for a sperm? Theoretically. But it supposes the woman's chromosomes (in the form of a pronucleus) will be pulled out of her eggs to make way for a second male set. It's hard to imagine many women falling for this one. Is it a substitute for a partner? Well, maybe, but one way or the other a vial of donated sperm is not hard to come by (WebPage 22), and it's much safer and cheaper. Is cloning ethical? If something is stupid enough, as cloning is, it hardly matters if it's ethical or unethical, but the ethical objections to reproductive cloning are comprehensive. On fundamental biological grounds it's the one technique described in this book that thwarts sexual reproduction, a pervasive, hard-won evolutionary development. On consequential grounds it's predicted to cause horrendous birth defects. And on social grounds it's almost universally condemned for its lack of obvious compassionate purpose and its potential for abuse at the hands of the state. Should doctors like Professors Antinori and Zavos (who achieved notoriety in the press during 2001 with claims they were to start human cloning, if necessary on an island in the Mediterranean Sea) carry enough try-hards with them to push their plan to fruition they'd better have paid careful attention to the forms their patients will need to sign to give informed consent. Even the mildest of the abnormalities that most cloned animals are showing will make for horrific press stories. Meanwhile whatever happened to the last guy who said he was going to clone humans … back in the year 2000? Where is Dr Richard Seed today? If Antinori and Zavos go the same place, there could be some disappointed lawyers. Stem Cell ResearchReturn to Top Ironically, a component of the cloning technology that gave rise to Dolly, the sheep, and which I am critical of in the previous section, could be the basis for the treatment of some difficult childhood and adult diseases, including diabetes and cancer. Stem cells are "primitive" or undifferentiated cells present in almost every tissue of the body, capable of (1) continuing to divide (by mitosis) without wearing out the ends of the cell's chromosomes, and (2) differentiating as required into mature, more differentiated, functional cells, to replace cells lost from tissue by wear and tear. The most undifferentiated stem cells are found in the embryo, in particular the inner cell mass of the blastocyst. Many scientists would love to research with these cells, but their availability is very restricted -- partly because lab conditions for embryo culture need to be excellent to obtain the blastocysts from embryos donated for the purpose, and partly because of limits on permissible embryo research (see Webpage 27). The hope is that these embryonic stem cells will be reliably induced to form more purposeful, differentiated cells that can be transplanted into diseased tissues or organs to replace faulty ones, thus enabling defective tissues to be repaired. At Sydney IVF we are working on such stem cells with the Diabetes Transplantation Unit of the Prince of Wales Hospital, Sydney, to develop insulin-producing cells that could be used to make up for a lack of them in children and young adults sick from juvenile diabetes, thus avoiding the need for frequent blood sugar measurements and insulin injections through the day and night. Similar strategies have been proposed to treat depleted bone marrow after chemotherapy for cancer, as well as possibly for adult degenerative diseases such as Parkinson's disease. Critics of embryo research claim that the same or similar outcomes might be derived from adult stem cells, which can, with some difficulty, be isolated from some tissues, and which might be able to be induced to de-differentiate further, then re-educated to develop into newly differentiated cell lines suitable for therapy. However, pursuing one research avenue in an area that is still so poorly understood without the simultaneous benefit of the complementary approach is like trying to try and walk or run on one leg. To invoke a different metaphor, if you are a map-maker surveying a landscape, think of the map you could make if you climb just one hill to look around at the surrounding valleys and hillocks. Then think of how much better a map you can make if you can climb a second hill to examine the same ground from a different perspective. The cloning technology that might be invoked involves somatic cell nuclear transfer, or SCNT -- the isolation of a partly mature cell from a differentiated tissue somewhere in the soma, or body, such as a breast cell (in the case of Dolly the cloned sheep) or a cumulus or granulosa cell (in the case of Cumulina, the first cloned mouse). The scenario I can envisage down the track is, say, an 18-year-old young woman, suffering from diabetes that requires 5 injections a day, or recovering from leukemia and requiring a bone marrow transplant that can't be found because of tissue incompatibilities and likely rejection. When SCNT becomes reliable and we know how to differentiate her embryonic stem cells, she would be able to undergo
And where is the ethical problem with that?
Copyright © Robert Jansen, W.H.Freeman and Scientific American Books (New York) and Allen & Unwin (Sydney) |