According to a recent report in the New York Times, the Department of Health and Human Services is “considering narrowly defining gender as a biological, immutable condition determined by genitalia at birth.” While the department’s memo purports to be “grounded in science,” the arguments and conclusions are not. Specifically, the memo argues that sex should be determined by—at different points in the purported memo—birth certificates, genitals and genetics. The problem with this argument is that none of these markers of sex is “definitive proof of a person’s sex” and in fact, nothing is. In reality, the course of becoming a “male” or “female” involves several steps, regulated by many genes and hormones.

Much of the time these processes all go in the same direction. But some of the time, they don’t. Seeing how that happens makes clear that the proposal, to define all people as male or female at birth, is scientifically dubious.

Our sex first begins to form based on our chromosomes, with most females having two X chromosomes and most males having one X and one Y. The official program for “maleness” is initiated by a gene called SRY. People with it begin the pathway to maleness while people without it start the pathway to femaleness. All infants start with neutral gonads and genitals, and both male and female internal reproductive organs. The SRY gene on the males’ Y chromosome turns the gonads of males into testes; without this gene the gonads become ovaries (with the help of additional genes). Insert a hormone, dihydrotestosterone (DHT), at high levels and our fetus develops a penis, scrotum and single opening for urine and sperm, while having low levels helps with clitoris and labia majora formation as well as the development of two openings corresponding to the vagina and urethra.

What isn’t as often mentioned is that at each of these (and several other) steps, the programming notes can get mixed up. Let’s start back at the chromosomes. It turns out that while most people end up with either an X and Y or two Xs, not everyone does. For example, some people get two Xs and a Y. Is such an individual male or female according to the proposed HHS changes? Studies suggest that most XXY individuals identify as men, but according to the purported memo, self-identification is not a consideration, only “genetic testing.” But what happens when genetic testing (i.e., chromosomes) can’t be categorized into male or female?

Moving along, let’s focus on individuals who are clearly either XX or XY. Remember, here’s where the SRY gene plays a role. Most often, the SRY gene is part of the Y chromosome, but sometimes, the SRY gene ends up on an X chromosome. Here now, you can end up with a person who has XX chromosomes, but whose body masculinizes, turning the fetus’ gonads into testes and activating high levels of DHT, through which a penis, scrotum and single opening for urine and sperm develop. Such individuals then have a clear, unambiguous categorization as “females” according to their chromosomes, but also have clear, unambiguous categorization as “males” according to their genitalia. Most of these individuals identify as men, and if you saw them you would likely agree, but in the memo’s alternate world, are these individuals male or female?

The reverse also occurs. Individuals with androgen insensitivity are “male” according to sex chromosomes and produce typical male hormones but have a genetic mutation that makes their tissues insensitive to the effects of those hormones, so they are born with “female” external genitals. These individuals usually identify as girls. As these cases demonstrate, using any one criteria—chromosomes, genitalia—or even using the criteria in combination can be problematic if one believes there are only two possible sexes and all indicators should produce one result.

We leave you with one final example. People with a condition called 5-alpha reductase deficiency have a genetic mutation that leads them to produce low levels of DHT. So, most are born with external genitals that appear female, despite having XY chromosomes. Historically, many were raised as girls and were even given birth certificates saying they are female. But, because hormones surge dramatically at puberty, their genitals become masculinized, and they develop male-typical characteristics, including a penis, deep voice, male-pattern public hair and male-typed muscle mass. Many of these individuals identify as men later in life. Thus, if we use genitals or birth certificates to determine sex, such a child could be categorized as “female” upon birth but by genitals would be “male” at puberty; if we use chromosomes to determine sex, the person would be consistently classified as a male. These individuals highlight yet another challenge to the memo: the notion that sex is “immutable.”

These cases, along with other known cases in which a person’s genitalia cannot be categorized as clearly male or female, are just a few of the many individuals whose identities are ignored by the memo and whose very existence—along with transgender people—calls into question the claims of the memo. Whatever criterion we use—genitalia, chromosomes, hormone levels and even birth certificates—can produce conflicting categorizations with the other criteria. We are not policy makers, but we can say that any policy that divides the world into two sexes—male versus female—will not be “grounded in science.”