From: Amara Graps (amara@amara.com)
Date: Mon Aug 12 2002 - 13:35:50 MDT
This man is famous for his scientific invention (the Pill), but
I didn't know before that he was such a talented writer too.
Science-in-fiction
http://www.djerassi.com/
One example:
http://www.djerassi.com/icsi2/index.html
<begin quote .. halfway down that page>
But to achieve a total separation of sex and fertilization requires two
components. The first is effective contraception - the virtual guarantee
of not creating new life during sexual intercourse. But this by itself
does not permit a complete uncoupling of sex and fertility; to
reproduce, one must still couple. Until recently, that is. The second
component is the extreme counterpart of the first - to create new life
*without* sexual intercourse. Our species achieved this capability in
1978 in England, through the birth of Louise Joy Brown. Louise was
conceived under a microscope, where her mother's egg was fertilized with
her father's sperm; the fertilized egg was reintroduced into the
mother's womb two days later, and, after an otherwise conventional
pregnancy, a normal girl baby was born nine months later. This technique
has since become widely known as in vitro fertilization (IVF) - an event
that has now been replicated at least 300,000 times through the birth of
that many IVF babies.
When Steptoe and Edwards developed IVF in 1977 they did not set out
deliberately to make possible the separation of sex from fertilization.
They, as well as other clinicians, were focused on the treatment of
infertility. Infertility is itself an ethically charged topic. To put it
bluntly and brutally, why should one treat infertility? From a global
perspective, there are too many fertile parents, hence there are too
many children, many of whom no one wants. The course of world history
will not change if no case of infertility is ever treated, but it will
change dramatically if excess human fertility is not curbed. From a
personal perspective, however, the drive for successful parenthood is
often overwhelming. Infertile couples are prepared to undergo enormous
sacrifices, financially, psychologically as well as physically, to
produce a live child under conditions where nature has made it
impossible. The question may well be asked whether the realization of
parenthood by biologically infertile couples carries some ethical
imperative-for or against. The enormous ethical dimensions of the
problem become somewhat easier to see if we consider the question of
male infertility. This issue was addressed in 1992, when a group of
investigators (Palermo, Joris, Devroey, and van Steirteghem) in Belgium
published a sensational paper announcing the birth of a normal baby boy
fathered by a man with severe oligospermia (insufficient number of
sperm). This child was made possible through the invention of an IVF
technique called "ICSI," for "intracytoplasmic sperm injection," in
which a single sperm under the microscope is injected directly into a
human egg. Whereas in the original English IVF work, the egg was flooded
with millions of sperm (as in ordinary sexual intercourse), with ICSI
the artificial insemination was accomplished with one single sperm. The
technology that makes such a fertilization possible also allows a
radical revision of the definition of infertility. ICSI can be applied
not only to men with low sperm counts, but to men who have *no mature
sperm whatsoever*. Such men suffer from an inherited condition of total
infertility, called "congenital, bilateral absence of the vas deferens."
The vas deferens is the duct connecting the testis to the urethra, and
is the organ where immature sperm mature. Without maturing in the vas,
sperm are incapable of fertilizing an egg; clearly a man with such a
condition can never become a father. But the barrier to fertility in
such a case is not genetic - even immature sperm possess all the genetic
material necessary to pass on a man's genetic heritage to posterity. It
is the machinery of mobility, and the enzymes that penetrate the egg's
cell wall, that are lacking. With ICSI, however, the machinery of the
laboratory can supply whatever the sperm lacks. One can aspirate
immature sperm directly from the testis and inject its DNA into an egg
under the microscope. Such fertilizations have been accomplished, and
numerous such men have now become successful fathers! Is this
acceptable? Does such an infertile man have the right to *demand* that
such reproductive technology be made available to him? And does it
matter what motivates such a demand? Does it make a difference if we
imagine we are settling the ultimate fate of a child-a concerned party,
certainly, but one whose concerns cannot be said to exist except as a
consequence of our decision? Or if we are simply satisfying a person's
desire to achieve immortality? And how does it change that question if
we consider what we are actually doing here - making the uninheritable
(i.e. genetic infertility) heritable?
This turns out to be more than an ethical quibble. In one case out of
four, men with "congenital bilateral absence of the vas deferens" are
also carriers of the gene for cystic fibrosis. With ICSI, one can
envisage a scenario in which such men could pass on to their offspring
both infertility and cystic fibrosis, raising the specter of successive
generations requiring ICSI in order to perpetuate their genetic
immortality-an immortality compromised by a disease that brings a slow,
early death.
The first ICSI baby is only 10 years old, but in that interval over
10,000 ICSI babies have been born. I have felt that the questions this
technology raises merit wider debate than the traditional venues of a
journal article or academic lecture allow. That is why I have
incorporated these questions first into a novel (*MENACHEM'S SEED* or
*MENACHEMS SAME*) and then into a play, entitled "*AN IMMACULATE
MISCONCEPTION*" ("*UNBEFLECKT*" in the German version). Here is an
excerpt from a scene of that play featuring a discussion between Dr.
Melanie Laidlaw, a reproductive biologist and (in the play) the inventor
of ICSI, and her clinical colleague, Dr. Felix Frankenthaler, whom she
had invited into her laboratory. After she informed him that she is
almost ready to perform the first ICSI injection into a human egg
(without, however, volunteering that she will pick her own egg for such
experimentation), they debate the possible implications of this work
beyond simply treating male infertility:
MELANIE
If your patients knew what I was up to in here· they'd be breaking down
my door. Men with low sperm counts that can never become biological
fathers in the usual way.
FRANKENTHALER
My patients just want to fertilize an egg. They won't care if it's under
a microscope or in bed· as long as it's their own sperm.
MELANIE
You're focusing on male infertility· that's your business. But do you
realize what this will mean for women?
FRANKENTHALER
Of course! I treat male infertility to get women pregnant.
MELANIE
Felix, you haven't changed. You're a first-class doctor· but I see
further than you. (Pause). ICSI could become an answer to overcoming the
biological clock. And if that works, it will affect many more women than
there are infertile men. (Grins). I'll even become famous.
FRANKENTHALER
Sure· you'll be famous· world-famous· if that first ICSI fertilization
is successful· and if a normal baby is born. But what's that got to do
with (slightly sarcastic) "the biological clock?"
MELANIE
Felix, in your IVF practice, it's not uncommon to freeze embryos for
months and years before implanting them into a woman. Now take frozen
eggs.
FRANKENTHALER
I know all about frozen eggs·. When you rethaw them, artificial
insemination hardly ever works·. Do you want to hear the reasons for
those failures?
MELANIE
Who cares? What I'm doing isn't ordinary artificial insemination·
exposing the egg to lots of sperm and then letting them struggle on
their own through the egg's natural barrier. (Pause). We inject right
into the egg· Now, if ICSI works in humans· think of those women-right
now, mostly professional ones-who postpone childbearing to their late
thirties or even early forties. By then, the quality of their eggs·
their own eggs· is not what it was when they were ten years younger. But
with ICSI, such women could draw on a bank account of their frozen young
eggs and have a much better chance of having a normal pregnancy later on
in life. I'm not talking about surrogate eggs-
FRANKENTHALER
Later in life? Past the menopause?
MELANIE
You convert men in their fifties into successful donors-
FRANKENTHALER
Then why not women? Are you serious?
MELANIE
I see no reason why women shouldn't have that option· at least under
some circumstances.
FRANKENTHALER
Well-if that works· you won't just become famous· you'll be notorious.
MELANIE
Think beyond that· to a wider vision of ICSI. I'm sure the day will
come-maybe in another thirty years or even earlier-when sex and
fertilization will be separate. Sex will be for love or lust-*
FRANKENTHALER
And reproduction under the microscope?
MELANIE
And why not?
FRANKENTHALER
Reducing men to providers of a single sperm?
MELANIE
What's wrong with that· emphasizing quality rather than quantity? I'm
not talking of test tube babies or genetic manipulation. And I'm
certainly not promoting ovarian promiscuity, trying different men's
sperm for each egg.
FRANKENTHALER
"Ovarian promiscuity!" That's a new one. But then what?
MELANIE
Each embryo will be screened genetically before the best one is
transferred back into the woman's uterus. All we'll be doing is
improving the odds over Nature's roll of the dice. Before you know it,
the 21st century will be called "The Century of Art."
FRANKENTHALER
Not science? Or technology?
MELANIE
The science of· A· R· T (Pause): assisted reproductive technologies.
Young men and women will open reproductive bank accounts full of
frozen sperm and eggs. And when they want a baby, they'll go to
the bank to check out what they need.
FRANKENTHALER
And once they have such a bank account· get sterilized?
MELANIE
Exactly. If my prediction is on target, contraception will become superfluous.
FRANKENTHALER
(Ironic)
I see. And the pill will end up in a museum· of 20th century ART?*
MELANIE
Of course it won't happen overnight·. But A· R· T is pushing us that
way· and I'm not saying it's all for the good. It will first happen
among the most affluent people· and certainly not all over the world. At
the outset, I suspect it will be right here· in the States· and
especially in California.
FRANKENTHALER
(Shakes head)
The Laidlaw Brave New World. (Beat). Before you know it, single women in
that world may well be tempted to use ICSI to become the Amazons of the
21st century.
MELANIE
Forget about the Amazons! Instead, think of women who haven't found the
right partner· or had been stuck with a lousy guy... or women who just
want a child before it's too late·in other words, Felix, think of women
like me.*
ICSI raises many other ethical and social problems beyond those
mentioned in the Melanie/Felix dialog. For example, now that the
effective separation of Y- and X- chromosome-bearing sperm has been
perfected, ICSI will enable parents to choose the sex of their offspring
with 100% certainty. For a couple with three or four daughters, who keep
on breeding in order to have a son, the ability to choose a child's sex
may actually prove a benefit to society, but what if practiced widely in
cultures (such as China or India) that greatly favor male children over
girls?
Or consider the capability of preserving the sperm of a recently
deceased man (say 24 - 30 hours post mortem) in order to produce
(through ICSI) a live child months or even years later-a feat that has
already been accomplished. Here we have immortality with a vengeance.
But what of the product of such a technological tour de force? Using the
frozen sperm and egg of deceased parents would generate instant orphans
under the microscope. The prospect is grotesque-yet does it take much
imagination or compassion to conceive of circumstances where a widow
might use the sperm of a beloved deceased husband so that she can have
their only child? These issues are intrinsically gray; the technology
occupies an ambiguous position, enabling us to enact our best and worst
impulses, and the answers cannot be provided by scientists or
technologists. The ultimate judgment must be society's, which, in the
case of sex and reproduction, really means the individual affected.
Ultimately, that individual is the child, yet the decision must be made
before its birth by the parents-or more often than we care to admit, by
just one parent.
It is the nature of such questions that they resist convenient
solutions, not least because of their tendency to proliferate faster
than we can solve them. Whereas reproduction has historically tended to
exemplify the law of unintended consequences, the addition of technology
has given that law added force. Consider: until very recently, the onset
of the menopause was welcomed by many women as the release from
continuous pregnancies caused by unprotected and frequently unwanted
intercourse. But the arrival of the Pill and other effective
contraceptives, coupled with the greatly increased number of women
entering demanding professions that cause them to delay childbirth until
their late thirties or early forties, now raises the concern that the
menopause may prevent them from becoming mothers altogether. Whereas
reproductive technology's focus during the latter half of the 20th
century was *contraception*, the technological challenge of the new
millennium may well be *conception* (or *infection*, if one focuses on
sexually transmitted diseases). In the long run, if the cryopreservation
of gametes followed by sterilization becomes a common practice,
contraception may even become superfluous. Melanie and Felix in the
above fictitious dialog were hardly the first to express such
speculation.
In 1994, in the scientific journal Nature, the cryobiologist Stanley
Leibo and I addressed the deplorable prognosis for a new male
contraceptive in the next few decades, given the total lack of interest
in that field by the large pharmaceutical companies without whose
participation such a "Pill for Men" could never be introduced. This led
us to propose an alternative approach, not involving the drug industry,
based on a few simple assumptions. Millions of men-admittedly, most of
them middle-aged fathers rather than young men-have resorted to
sterilization (vasectomy) and continue to do so. The procedure is much
simpler and less invasive than tubal ligation in women. (Sterilization
among both sexes has become so prevalent that in the U.S., it is now the
most common method of birth control among married couples, even
surpassing the Pill). Artificial insemination is both simple and cheap.
Furthermore, among fertile couples, it has almost the same success rate
as ordinary sexual intercourse. But most important for our argument,
fertile male sperm has already been preserved inexpensively for years at
liquid nitrogen temperatures. Therefore, provided one first demonstrated
that such storage is possible for several decades rather than just
years, some young men might well consider early vasectomy, coupled with
cryopreservation of their fertile sperm and subsequent artificial
insemination, as a viable alternative to effective birth control.
Shifting more of that responsibility to men, at least in monogamous,
trusting relationships, appeared to Leibo and me a socially responsible
suggestion. I shall spare the readers a record of the resulting
outcry-both by media and in personal correspondence-but a lot has
happened in the intervening few years to make it much more likely that
such a prediction will become fact within a few decades rather than
dramatic license.
Although many may consider some of the scenarios raised in *AN
IMMACULATE MISCONCEPTION* as "unnatural" or worse, every one of them has
now been realized or is about to be implemented. Take the question of
post-menopausal pregnancies. In progressively more geriatric societies
(for example, in Japan or Western Europe), where 20 per cent of the
population is already or will soon be over the age of sixty, and older
people are increasingly healthier than they used to be, a woman who
becomes a mother at 45 could raise a child for a considerably longer
time than could a 20-year-old at the beginning of this century. Of
course, motherhood at an older age is physically, psychologically, and
economically suitable only for certain women, but at least the choice is
now available in wealthy countries. It must be emphasized that this
increased emphasis on artificial fertilization techniques and even
surrogate parentship is a characteristic of the affluent, "geriatric"
countries. Even within these countries, the cost of such reproductive
technologies (frequently not covered by insurance) is such that only the
more affluent citizens can afford them. Three-fourths of the world's
population are represented by the "pediatric" countries of Africa, Asia
and much of Latin America, where over 40% of the population may be below
the age of fifteen and where the control of fertility rather than the
treatment of infertility will remain the catchword for decades to come.
I have deliberately refrained from considering the implications of human
cloning-the closest technological approach to immortality. But to the
extent that biological parenthood is a form of immortality-admittedly
one subject to mutational and hence evolutionary adjustments-IVF tampers
with that as well. In the excerpt from my play, I allude to
pre-implantation embryonic genetic screening, again a procedure
primarily available to the affluent in the affluent countries. But soon,
the entire human genome will be elucidated. Given the many technically
feasible methods of rapid genetic screening, what will keep prospective
IVF parents from screening their own embryos so as to transfer only the
"best" back into the mother? Who will define "best"? Few people will
argue that prospective parents may wish to discard embryos that show the
markers for Down's or Huntington's Syndrome, or markers for genetically
transmitted cancers, but where will the line be drawn? Short stature?
Left-handedness? Big ears? As we move in the direction of tailor-made
progeny, the gulf between the haves and have-nots is widening
enormously.
The recent advances in contraceptive and reproductive technologies have
clearly raised a multitude of gray problems which many of us would like
to wish away. But that is not possible anymore - the genie has escaped
from the bottle. Legislation will not offer a solution, unless it were
global in nature. Otherwise, a committed couple-or perhaps just the
woman-will cross geographical borders in an attempt to circumvent
biological ones. The answer is intensive and continuous debate, based on
knowledge rather than myth, which is one of the reasons why I, the
scientist, have moved to fiction and drama as novel ways to raise the
intellectual level of public discourse of sex and reproduction.
<end quote>
Relevant literature by Carl Djerassi
"Menachem's Seed", Penguin-USA, New York. 1998
"Menachems Same", Haffmans Verlag, Z¨rich. 1996
"NO", Penguin-USA, New York. 2000
"NO", Haffmans Verlag, Z¨rich. 1998
"An Immaculate Misconception", Imperial College Press, London. 2000
"Unbefleckt", Haffmans Verlag, Z¨rich. 2000
"The Pill, Pygmy Chimps, and Degas' Horse", Basic Books, New York. 1993,1999
"Die Mutter der Pille", Haffmans Verlag, Z¨rich. 1992, 2000
"Von der Pille zum PC", Haffmans Verlag, Z¨rich. 1998
C. Djerassi and S.P.Leibo."A New Look at Male Contraception", *Nature*,
370, 11. 1994
--
********************************************************************
Amara Graps, PhD email: amara@amara.com
Computational Physics vita: ftp://ftp.amara.com/pub/resume.txt
Multiplex Answers URL: http://www.amara.com/
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"Drosam pieder pasaule." (The world belongs to the brave.)
--a Latvian proverb
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