Separating The Boys From The Girls / Sex-selection advances in animals undergoing trials in humans - Newsday, Sept. 1, 1998

By Robert Cooke. Staff Writer

Think of it as sex on demand, but not that way.
     Selecting sex, as in having a girl or a boy baby, is becoming a commercial reality - the many ethical and social questions notwithstanding. Several companies - one for cows and horses and another for babies - are now performing sex selection by accurately sorting sperm well in advance of conception.
     A least one baby has been born of sperm selection as practiced by a Virginia firm, Genetics and IVF Institute. And a member of the staff, Edward Fugger, said, "We currently have a clinical trail ongoing in humans."
     In the meantime, a small Colorado biotechnology company, XY Inc., recently announced it has produced the first horse through sperm sorting. Named Call Me Madam, the filly was born Aug. 6. The achievement is expected to have large impact on the practice of horse breeding.
     Furthest along is sex selection in cattle, where dozens of animals have been born after sperm was sorted by sex.
     "We've got 28 pregnancies, and 27 of them are the right sex," said physiologist George Seidel of Colorado State University in Fort Collins. "The year before, we had 19 calves born from this [sex-selection process], and 18 were of the correct sex." Seidel is affiliated with XY Inc. as director of science.
     At present, he added, "we aim for 90 percent" accuracy in producing one sex or the other on demand.
     The technology for sorting sperm reliably was invented just a decade ago by Lawrence Johnson and his colleagues at the U.S. Department of Agriculture's main research facility in Beltsville, Md. Johnson has been working on animal reproduction for 35 years.
     "The breakthrough came in 1989, when we could separate living sperm and then use them for in vitro fertilization," Johnson said. Sex selection was first achieved in rabbits, "then in pigs, then in cattle and sheep."
     The USDA subsequently licensed the technology for use in non-human mammals to XY Inc. and to a company called MasterCalf in England. MasterCalf has since been acquired by XY Inc.
     The right to use Johnson's sperm-sorting technique for human reproduction was licensed to Genetics and IVF Institute in Fairfax, Va., which reported the birth of the sex-selected girl in 1994.
     Johnson said that most recently his team at the USDA Agricultural Research Service has greatly sped up the sperm-sorting process.
     "We've had some improvements in the technology that allow us to produce 5 million sperm per hour. That's 10 to 12 times greater than we had a couple of years ago," Johnson said. With ample sperm, it's possible to get pregnancies via artificial insemination, rather than the far more difficult process of in-vitro fertilization.
     The sperm-separation technique is based on a subtle biological difference between male and female sperm cells. Female sperm carry an X chromosome, and male sperm carry a Y. The X chromsomes are bigger - they contain more DNA - than Y chromosomes, and that subtle difference can be exploited.
     To sort sperm according to sex, the mixture of Xand Y-bearing sperm is treated with a special DNA dye that fluoresces - glows - when illuminated by a laser light. The tiny cells are then pushed through a very narrow tube, and each sperm cell glows as it passes through the beam of laser light.
     Those that glow brighter are the female sperm cells. A computer, reading brightness levels, alters the electric charge in a steering mechanism, shunting the female cells and the male cells into different dishes. Sperm cells that are "indeterminant," not glowing enough to tell the difference, are dropped into a third container. This separation process is called flow cytometry.
     With cattle and horse sperm, the difference in brightness between male and female sperm cells is about 4 percent. In human cells, the difference is only 2.8 percent, so human cells are significantly more difficult to separate, Johnson said.
     According to Dr. Mervyn Jacobson, who heads XY Inc., production of the filly Call Me Madam is an important achievement.
     "Selecting whether a horse will be female or male before it's even conceived will revolutionize the horse industry," he said. "To produce a beautiful, live foal whose sex was predetermined 11 months earlier is a first on many fronts - scientific, economic and ecologic," Jacobson said. "We're elated."
     There is a strong preference for different sexes in different equestrian sports, he explained.
     "If you're in the horse business for polo" in South America, for example, he said, "they only want females; they trash the males." At birth, almost all polo ponies born male in South America are regarded as no better than garbage, he said.
     Alternatively, "if you're a performance horse breeder, say for jumpers in Europe, then you want males," Jacobson said. The most successful jumpers are usually male because of greater strength and muscle mass, he said.
     Generally speaking, in the United States "all serious horse breeders," including those of quarter horses, Morgans, Arabians and a few others, have strong preferences for which sex they want. So gaining a reliable way to select for sex will be very useful and widely exploited, he predicted.
     Thus the birth of Call Me Madam "is truly historic. For 5,000 years people throughout the world have yearned to determine the sex of their animal herds," Jacobson said.
     The economic returns from sex selection for other livestock should be even larger. In cattle, for example, dairy farmers want mostly cows to be born, rather than bulls. So if the sex ratio can be skewed to make almost all of the calves born female, the number of pregnancies needed to build a herd will be perhaps cut in half. Normally, the male-to-female sex ratio is close to 50-50, and the bulls from dairy herds are quickly sent off to be raised for veal.
     "We know that about 10 million dairy calves annually born male are slaughtered at birth," Jacobson said, because bulls are useless in the milk business, except for a very few needed for breeding, for sperm production.
     Similarly, beef breeders prefer males, and breeding only to get big, muscular bulls could significantly improve profits for the meat industry, the researchers at XY said.
     "The waste from unwanted sexes in animal breeding industries is enormous," Seidel added. So being able to select for sex should turn out to be important. In fact, Seidel is striving to get the sperm-selection technique down to very low cost, as low as $10 per cow. "But we may not get there; it might be $20," he said.
     For horse breeders, however, Seidel predicted the cost "is going to be a lot more than that. Horses require a lot more sperm" for artificial insemination, and the numbers of horses that will be bred are far smaller; "they won't be breeding millions of horses."
     As a result, Seidel thinks the cost per horse for sperm sexing will be substantial: "I think we're talking more on the order of $1,000 for a horse."
     No cost can yet be estimated for sperm selection as a practice in human reproduction, because so few attempts have been made. But as the technology progresses, it's likely the improvements in animal physiology and human reproduction physiology will be shared back and forth between animal laboratories and human clinics. Indeed, many of the advances that have come to animal breeding were first devised by scientists working on human reproduction.
     For now, "in cattle, we're still working on faster and more efficient flow cytometers," Seidel said. "We've now combined sexing and freezing [of sperm], and the initial results are promising." Frozen sperm can be held indefinitely, so breeders can use the sex-identified sperm exactly when needed.
     Using sperm-sexing technology for human reproduction, however, is fraught with ethical and social pitfalls. Some observers worry that natural sexual balance - the almost 50-50 ratio of males to females - may be grossly disturbed if people are given the power to select their offspring's sex.
     "The problems could range between nothing to causing some problems with gender imbalance" in the national population, said bio-ethicist Thomas Murray of Case Western Reserve University in Cleveland.
      Murray said the distinction between sperm selection and sex selection is important, because sex selection - as practiced already - usually involves aborting a fetus of the "wrong" sex. "People have done that" via abortion, Murray said, and "it causes a considerable amount of discomfort among genetic counselors." In fact, some counselors refuse to participate when the goal of genetic testing is sex selection, he said.
     As for sperm selection, Murray said, ethically "the concern is that this is an entering wedge to the kind of future world where we make children by design. Where we might not only choose the sex we prefer, but other characteristics such as hair color, eye color and other factors that are under genetic control."
     Others see major markets for human sex selection - via sperm selection - in Asia, where there are strong traditional preferences for male babies, where, indeed, the cruel disposal of girl babies is a long-standing problem.
     Murray, author of a recent book, "The Worth of a Child," said it's not clear "whether it would be a good thing for us as a country if people were able to exercise fairly extensive control over the [genetic] traits of their children."
     Seidel, asked if there is any danger, say, for birth defects from the sperm-selection techniques, replied: "There is some concern about that. When we freeze semen we damage the sperm" to a small degree. "And when we sex them we damage them as well, but not as much as in the freezing process."
     In any case, he added, "the damage is not severe," and no hints of developmental problems have been seen with the sex-selected farm animals born so far, or in the baby girl born of sex selection.

Copyright 1998, Newsday Inc.