MIKE: Mr President, its very kind of you to meet us.

PRESIDENT: Do thank my secretary for arranging this time for our meeting. I was told that you did not wish to disclose the details of our meeting; I assure you that this is not on record. MIKE: It is good to meet you again Professor Harter, a National Science Advisory Board pathologist could assure the president that what we are about to discuss is accurate. [Professor Harter frowns at the implication] MIKE: Let me do the introductions, Im Michael Simmons, doctor of genetics. This is Sally McFinn, doctor of sociology and economics. This is Daniel Nicklow, doctor of developmental psychology. [Dr Nicklow looks around idly] PRESIDENT: What did you wish to discuss then? SALLY: I will present this as objectively as possible. What we are about to explain concerns the security of the entire human race. Dont look up Mr President; there isnt a rock about to drop on us. There is more than one way the human race could end. Right now, we are facing just such a situation. HARTER: An epidemic? That would explain why you asked specifically for me to attend this meeting. SALLY: [coughs once] Ahem, yes, it is similar. Mike, I know you know its not quite the correct distinction but it is a good analogy. Last year, I was running the results of a population survey through a computer analysis program to look for trends. One of them was a slight decrease in gender ratio in the last ten years. To be precise, the gender ratio at birth has dropped steadily from 1.05 males to 1 female to 1.02 males to 1 female. PRESIDENT: We know about that. CIA investigated it but there appeared to be no evidence for any problems. SALLY: When I investigated this trend, thinking that it might give interesting results, I found a factor. The drop in ratio is associated with states closer to Washington, decreasing the further away you get. The geographical distribution is represented in colour here. I hope it is obvious to you. I sought Mikes help, and we took DNA samples from ten volunteer mothers and sequenced them using the new high-throughput sequencing. The computer found an insertion in the human genome. MIKE: I investigated this and found an interesting mobile genetic element that was coding RNA. This element occurred multiple times through the chromosomes in the people in which its present. It is always present either in high numbers, all more than 10 copies, or none at all. This genetic element is directly correlated with female birth.

SALLY: 100% correlation in fact. Mothers who have this gene always give birth to female children. Currently, less than 1% of mothers carry this gene. Im sure you see why there are no male carriers of this. HARTER: That is all very interesting, but with only a sample of 10, surely it must be an anomaly? [Sally looks flustered] MIKE: [clears throat] Well, after such a finding, we wanted a confirmation. I stole blood samples from a colleague who was developing a rapid antigen recognition method. We tested them for the genetic element and added it to our data. [Harter looks shocked] PRESIDENT: Thats illegal. You determined peoples DNA without consent and retained personal data. Do you realize that I cannot overlook that? MIKE: [nods in agreement] That is correct. But as I am about to explain, you will be very glad we did this. The genetic element carries a transposase, which is unimportant, and an RNAi. The RNAi expression is controlled by SRY and causes interference with the expression of one of the ribosomal 30S proteins. This interference is lethal. Data is here. [Mike takes out a bound folder and hands it to Harter] [Harter looks even more shocked and scans data quickly] PRESIDENT: Professor Harter, is this a serious matter? [Harter nods, looking calmer and deathly serious] PRESIDENT: Excuse me. [the President walks to the side and calls his secretary] PRESIDENT: Cancel the appointment with the Sinian Oil Industry Group, I will not be there... ... Ok fine, Ill talk to them myself. [the President walks back to the table and sits down] PRESIDENT: I am not a biologist. Could you explain to me the conclusion of your findings? Harter, do please confirm them for me. MIKE: The SRY gene is short for Sex-determining Region Y. It is the gene that is present only in males and determines maleness. Our genetic element has a lethal product that is only expressed in males. Male zygotes with the genetic element do not survive. PRESIDENT: That explains the drop in sex-ratio then.

MIKE: That is correct. The lethal gene is completely silent in females. They develop completely normally except for a marginally higher mutation rate. Also, the genetic element copies itself randomly in the genome. Multiple copies exist and with an elevated but not deleterious mutation rate. The chance of a carrier having all defective copies is negligible. There is also a very high chance that all the children of these mothers will carry the genetic element. An overwhelmingly high chance. SALLY: The gene essentially makes all children of carriers female. And all children are carriers. A friend did a theoretical analysis, the gene will spread throughout the population and eventually there will no more men. This is estimated to take around 200 years to reach just over 50% carriers. PRESIDENT: Extinction of the human race? Harter, do you think you can confirm that? [the Presidents phone rings] PRESIDENT: Excuse me, I have a meeting to cancel, pardon my absence. [the President leaves] Mike, Sally and Harter discuss the data. Daniel samples the tea and cookies and looks bored [the President returns and looks at Harter expectantly] HARTER: [choosing his words carefully] Yes, if their data is trustable, I can confirm that the situation they describe is plausible. PRESIDENT: So were doomed to have more and more women until the population dies out? SALLY: Yes. PRESIDENT: This merits a state of emergency. Ill like to thank you two... three for your audacity in violating the law, without which we could not have known of this crisis. Ill see what I can do to mitigate your sentence. DANIEL: Mr President, with all due respect, you must not exercise your presidential power on this matter. [Everyone looks at him] DANIEL: I assume, Mike, that you did not publish a paper concerning this given that that would land you in jail. Is this correct? [Mike nods] DANIEL: That means we five people here are the only people who know about this imminent crisis that will make itself clear with increasing speed over the next generation. Although the truth will out eventually, we must delay that time as much as we can and prepare for society to receive such a truth. PRESIDENT: What do you mean? I think creating a national board to inquire into this problem will help solve it. We have 200 years after all.

DANIEL: Think about what it means and whatll happen to society should the news leak out. You must have experienced lobbying before, having run for Presidency. How do you think feminists would react to this? Or the Catholic Church? Institutions that are inherently sexually biased will be... [the President begins to interrupt him but Daniel continues] DANIEL: There is no need for me to be politically correct here. You know they are biased. Why are there no female Catholic priests? What do you think will happen when they realize there will be no more men to choose from? [the room is silent] PRESIDENT: We need solutions to this problem. Do you mind staying for the next few hours? ... Good.

Ending 1 HARTER: The analogy to an epidemic is very clear. Except that the transmission only occurs from mother to child. Things that work against diseases will work here. Quarantine. DANIEL: Think about what happens when people think that they are about to be forced to check for this genetic element and be placed into quarantine with no chance of children? Or killed outright? [the President looks worried] SALLY: You cant implement it. Itll never work. Even with just under 1% carriers, there already too many of them. PRESIDENT: What do you think would happen if we tried? DANIEL: What measures would this quarantine require? The carriers cannot be cured; it is not a disease in the normal sense. You will have to quarantine 1 million women, and initiate tests throughout the population. Quarantined carriers cannot be allowed to have children. [the President looks on silently] DANIEL: [looks a little discomfited, for the first time] Assuming Congress doesnt kill the bill first. Mass protests, not just from carriers, at least their husbands as well as sympathizers. Breakdown of law and order, possibly having to mobilize the military. Forced testing of population, possibly needing to criminalize failure to get tested. ... Mass violation of human rights and resurgence of racism against carriers. Since carriers are all women, incidence of crimes against women will rise as the population changes its mindset. Furthermore, since the gene will have moved overseas by now, you will need to keep up the effort. Not all countries will impose it, and if I understand this properly, just a few people slipping through can start the epidemic again. Not feasible.

Ending 2 SALLY: We could attempt to keep numbers up with family planning though. By encouraging noncarrier women to have more children. DANIEL: [grins and says sarcastically] Preference due to genetics? True racism? In America?

Ending 3 MIKE: With a few years work, and a genetic lab, I could engineer a similar genetic element that would deactivate the transposase and restore it to Mendelian inheritance patterns. If spread through the human population, it could prevent the lethal genetic element from ever becoming more than a rare genetic disorder. DANIEL: Genetic modification of the human population could be the best solution.

Ending 0

Cloning / asexual reproduction o o Making Sperm and Egg cells from female skin cells Clone males

pure colonies set up and males exported Sperm bank, egg bank of non-carriers, if replace more than half the carriers children, gene will be suppressed One/no child policy for carriers, 3 child policy for non-carriers, gene is suppressed o Forced sterilization of carriers

Viral vector destroys lethal gene through homologous recombination