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Four articles by the venerable science journalist Sebastian Shaw, from the years 2030, 2040, 2055, and 2070:
January 7, 2030
Facetweet Times "Detecting Genetic Defects Earlier Than Ever" Sebastian Shaw
To learn more about the latest reproductive screening technology, I followed a woman I'll call Aspen on her visit to the Obstetrics and Gynecology center at Mass General Hospital. A 33-year-old professional, she arrived four days after she ovulated. A technician wielded a device the size of a hand vacuum cleaner. The business end was a flat plastic plate the size of an old music CD, and she placed it on Aspen's bare stomach just above her pubic bone. After 30 seconds the technician determined that she did indeed have a fertilized egg on its way down the fallopian tube to her uterus. Aspen was visibly pleased at the good news.
Her expression turned more somber as the technician prepared her for the next step. She had not come here for simple good news -- she was here to rule out bad news that might not be simple.
The ability to detect genetic diseases in a fertilized egg four days after ovulation rather than seven days after is not that important to most women. But to some who are uneasy with abortion, implantation is a key milestone. If the egg is destined to produce a child with a disease, then when an egg is just passing through the uterus, it's not so bad to just let it keep going. Once it has put roots down, it's a harder choice.
Watson and Crick discovered the double helix of DNA in 1953. After decades of intensive scientific efforts, gene sequencing became possible. The human genome was first fully sequenced in 2003, a half-century after Watson and Crick's discovery. This was just one milestone in a research effort that held high promise for saving human lives. But fundamental advances have been slow to yield practical benefits -- many start-ups failed when a marketable product proved to be out of reach. Now the benefits are clear and significant, and with the benefit of 2030 hindsight -- 2020 hindsight is a decade behind us now -- we can see all the obstacles that had to be overcome to move from sequencing the human genome to practical applications. Now we can detect most common errors in the human genome early, when abortion is still possible.
The National Medical Database tells us that in the US, the incidence of genetic diseases has dropped dramatically. The ability to detect massive genetic abnormalities such as Down Syndrome has been around far longer, but now diseases caused by a single errant nucleotide can be reliably detected in the early stages of pregnancy. New cases of cystic fibrosis, Tay-Sachs, Huntington's, Sickle Cell Disease and many others are down sharply. They could be virtually eliminated if two additional conditions were met. One is universal access to high-quality medical care. The other is the willingness of mothers to abort a fetus with an abnormality. The second is of course a moral question, not a medical one. Many women refuse to have the genetic testing performed; even after a serious genetic disease has been diagnosed, about 30% of mothers carry a pregnancy to term.
Some women are unwilling to have an abortion from the moment of conception, usually on religious grounds. For others, unwillingness rises as the fetus becomes larger and more developed. Studies show that in practice, a woman's decision is most strongly influenced by the invasiveness of the abortion procedure -- and advances in technology have made it less and less invasive. A 4-month pregnancy can now be terminated with an hour's procedure under IV sedation and virtually no side effects. The woman's experience is going into a hospital pregnant, falling asleep, and waking up with no signs she can detect that she ever was pregnant.
Earlier-stage pregnancies can be terminated by taking one pill and having a heavy period -- without even the menstrual cramps that most women before the year 2023 considered an inevitable monthly occurrence.
Still, there is a drive for ever-earlier detection. Doctors used to rely on amniocentesis, but this requires the presence of a fair-sized amniotic sac. For the past 8 years or so they have needed only a maternal blood sample to fully sequence a fetus's DNA -- once it has implanted.
Now nearly finishing clinical trials is a technology that allows DNA sequencing before implantation. Aspen is one of the patients in the trials. Having determined that her egg had been fertilized, it was time for the real test.
The sensor was an impressive belt, six inches high, an inch thick and weighing about ten pounds. Given the current state of technology, that is space and weight to hold a lot of sensors -- the sensing power of 4,000 MRI machines of 2010 vintage. Aspen sat in an ordinary armchair as the technician wrapped the belt around her hips. All she had to do was sit still for twenty minutes. After five minutes, as our conversation tapered off, she elected to read. Electronic devices interfere with the sensors, so she read a book -- the old-fashioned kind based on Gutenberg technology.
The other presence in the room was a computer on a cart. Imagine a stack of four microwave ovens. This enormous computing power is required for an astonishingly complicated task. Aspen's fertilized egg had by now divided many times into a ball of cells. The computer needs to detect the minuscule vibrations of the nuclei of the atoms in that little ball, and from that determine the exact sequence of 3 billion base pairs in the simple CGAT genetic code. The mass of surrounding maternal cells all have the same DNA sequence, a background against which this tiny ball of cells is a very faint signal. The computer takes advantage of knowledge of the father's genome, but it is still a very difficult problem.
Once the test was done and the belt removed, Aspen and I were ushered into a doctor's office. A minute later Dr. Michelle Renaud entered, introduced herself, and started talking.
She had bad news. The ball of cells had a genetic abnormality that was inconsistent with life. It might or might not implant, but it would not live long enough to really count as a pregnancy. If Aspen did nothing, she might conceivably miss one menstrual period. But her body would shortly flush out this tiny blob of dead cells. Without the test, a delayed period would just tell her she hadn't gotten pregnant. About a fifth of failures to conceive during any given month are due to problems of just this sort. This result had no adverse implications for Aspen's ability to have a normal baby in the future.
The good news was that she had no life-and-death decision to make about whether to bring a child into the world. Her only choice was whether to take a morning after pill (the newest versions of which have no side effects at all) or let nature take its course. She took the tiny generic pill with her and was told she had a day to take it if she wanted. She scanned a QR-X code with her wristy which would give her access to further information on the situation in however much depth she wanted.
I reached Aspen by phone a week later. Asked how she felt about the experience, she said it was a little disconcerting to think she had produced something so very defective, but well worth it. She planned to go back every month until she did conceive a health baby.
I accompanied three other women that day. Two did not have any fertilized egg at all and never made it to wearing the heavy belt. The fourth was a petite 28-year-old redhead I'll call Martha. She is married to a woman, and was having the test four days after artificial insemination. She went through her half-hour with the belt and was told she had a healthy baby. The test's job is to verify that all the important genes are healthy. But in the process, it inevitably also reveals which healthy variants of those genes are present. A few of them have simple effects. Martha wanted to know, and was told she would have a girl with brown eyes and A-positive blood.
When I followed up with Dr. Renaud, she reported that for Aspen's defective ball of cells the underlying technology could reveal the gender, blood type and eye color it would have had if it had been viable. But revealing those "what-ifs" was not going to be comforting, so the software is configured in the factory to destroy that information once a "not viable" diagnosis is made.
It was no surprise that none of the four patients I followed that day was on course to deliver a baby with what we usually think of as a genetic defect -- since the nonviable ones don't enter our everyday thinking at all. What we call genetic defects are quite rare and always have been.
When this technology emerges from final tests and becomes publicly available, scientists predict more women will choose to have the test and more will abort in case of a defect. In parallel, the genes for ever-rarer diseases are being identified. We will continue to hunt genetic diseases towards extinction.
Another promising technology is in its infancy. It should be possible to apply the same sensing technology earlier, before conception. There is no sperm in the picture yet, but the test could detect the half of the genome that would be contributed by a ripening egg. If the egg has a defect, the couple might just decide not to invite any sperm to meet that particular egg, a decision that is acceptable to most people who are opposed to abortion -- and beneficial to many women like Aspen who would not allow a defective ball of cells to implant but would feel morally uneasy about it.
Although no sperm have met the egg in this test, such a calculation could take into account the genome of the prospective father. In a fairly common case, the chances are 50% that he would contribute a gene causing a defect and 50% that the baby would be normal. A different father might with certainty contribute a working copy of the relevant gene, guaranteeing a genetically normal baby.
March 21, 2045
Facetweet Times -- "Genetic knowledge, computing power, and humongous data combine to let us predict your baby's adult face" Sebastian Shaw
In the late 20th century, doctors could tell from amniocentesis whether a fetus would have Down Syndrome and whether it would be a girl or a boy. That could be done by just looking at the 46 chromosomes. In the one case they were looking for an extra chromosome, in the other looking for a small Y instead of a large X. Only in the 21st century have we been able to look within the 46 chromosomes at 3 billion base pairs to find the defects in individual genes. A genetic disease in a newborn baby today in the developed world is extraordinarily rare. The cases that do occur are largely confined to children of religious fundamentalists, including devout Catholics.
But scientists can find more than gender and defects. Sometimes things go wrong, but most of the time they go right. Genes determine healthy variation too. A decade ago it was easy to determine from a noninvasive scan of a tiny ball of cells the eye color and blood type. Good guesses were soon possible for height and hair color. Intelligence joined the mix, and this posed a new problem -- an ethical one. Most people would consider very low intelligence a defect. But depending on parental expectations, anything short of very high intelligence could also be viewed as a defect. There is no clear line between a defect and healthy variation.
The danger of genetic knowledge leading to eugenics occurred to thoughtful people long before it became a technical possibility. As a reaction to recent advances, legislation has been enacted or is pending in many states that limits the information that doctors can convey to prospective parents. Given the enormous complexity of prenatal DNA sequencers, prohibitions have been largely effective in the case that matters -- when abortion is still a possibility.
But once a baby is born, there are no such restrictions.
We have heard for some time now of predictions of intelligence, height, strength, coordination, and running speed, for instance. The predictions keep getting more accurate.
Then we heard of predictions of the six key personality traits: openness, conscientiousness, extroversion, agreeableness, neuroticism, and the recent addition: optimism.
But massive computing power, the DNA sequences of a billion people, and plain old digital photography are allowing something quite different: predicting what someone is going to look like.
I joined Dr. Aaron Singh in his lab at Carnegie-Mellon University. A short, dark-skinned man with a ready smile and perpetual twinkle in his eyes, it was impossible to miss his enthusiasm for his work.
"Here are some examples of what we were able to do last year," he said, bringing up a series of side-by-side pictures on his 36-inch monitor. The first pair of pictures was the same blue-eyed woman with short dark hair. Or that's what I would have sworn. Maybe they could have been identical twins instead of the same person. But Mr. Singh told me that the picture on the right was the real woman at age 26. The one on the left was derived from nothing but her genome, some very complicated algorithms and a great deal of number-crunching. My jaw dropped. Next he showed me the same woman aged backward in time. My eyes saw two pictures of the same 8-year-old girl. Up next was a pair of African-American men of 52 years. He asked if I could tell which was the real picture and which the simulation. I had no idea. He grinned at that, but noted that the level of realism was an older advance -- the current problem was how to produce accurate predictions, not simply ones that were realistic in every detail.
These results were astonishing. "That was last year?" I said.
Dr. Singh laughed. "Well, I have to admit I showed you my very best examples. Here are some of the worst..."
They were indeed bad. A broad face and big nose in one case, a narrow face and much smaller nose in the other.
"But what we care about most is the average case. And I'd like to show you the results from our latest study."
More pairs of pictures came up. For these I would have judged the two people to be brothers or sisters -- a definite family resemblance, but different people. I then saw a picture of Dr. Singh and the prediction based on his genes, and could definitely tell which was Dr. Singh.
Next I saw a pair of earnest-looking 4-year-old East Asian boys who again looked like identical twins. "Our predictions are best with children," he said. "People naturally diverge from predictions as they get older. To some extent that's just more genes doing their work differentially, and partly it's environment. Take a look at these." I saw what I correctly guessed were the same boy, now at age 45. But those images looked quite different, one looking well-preserved and the other more worn down. "We're toying with adding in environmental factors. For instance, most of our Japanese data is on people who live in Japan -- not surprisingly. But this man actually grew up in New Delhi, eating New Delhi foods and breathing New Delhi fumes. If we put in our environmental model, you can see the results." The match was noticeably better -- now both looked worn down.
I saw pictures of our US President Kyle Connor -- a decent match.
Finally I saw two pictures of myself -- or me and my predicted alter ego. I had given him access to my genome in advance of the interview. Looking at the simulated face was a creepy experience. Who was this other guy? Is that who I should have been? He actually looked like me -- like the big brother who the younger one can never quite compete with. Perhaps sensing my discomfort, he said, "But then there's this," and I saw next to the real me a much less appealing man -- the dissolute ne'er-do-well of my imaginary clan.
"That's you on a traditional Russian diet."
I asked if he could describe the advances -- what had led to the improvements and what would lead to more. "Schwartz-Feingold Hidden Markov Models" was the first in a long list. The algorithms are beyond the comprehension of more than a couple dozen experts worldwide. But I did get the picture that there were still plenty of interesting ideas to try and he was confident of further progress.
I tried to think through what it would mean to have accurate pictures -- to know what your baby will look like at the age of 50 -- or 90. I asked about predictions for old people, and I thought I saw his face darken for one brief moment before it resumed its bright smile.
"Those results aren't so good," he said. "And to be honest, we're not focusing our efforts there."
The implications for parents seeing their newborn at age 50 were plenty of food for thought. We have always been uneasy at the prospect of knowing too much about our future. On the bright side, I figured that some awkward 13-year-olds could be relieved to see themselves at 21.
February 12, 2055
Apple Micro-Google Times "The Quest For Uniform Sperm -- How and Why" Sebastian Shaw
I have interviewed many intensely driven scientists over the years, but Dr. Kyle McCarthy stands out.
We met in his office at the giant medical complex in Atlanta, Georgia. He is notably clean-cut, and a conservative dresser -- formal Scottish wear, largely unchanged from the 18th century: kilt, matching sash, Prince Charlie jacket, and sporran. He is also a devout Catholic. Church attitudes on homosexuality and the inclusion of women have softened in recent years, so if there is one thing that defines a Catholic today, it is an implacable opposition to abortion of any kind. It is the most fundamental conviction of his faith: human life begins at the moment of conception, and any human intervention to end that life is murder. He is not the least apologetic in admitting that it has driven his life's work.
In the early days, the practical application of advances in genetic knowledge started after birth. It was limited to predicting future disease and providing early treatment. But sensitive scans inside the mother allowed detection of defects in tiny fetuses. A mother who didn't want a child with a defect could get an abortion. As technology has advanced, the new life's genome can be known earlier and earlier. Now it is routine to abort small balls of cells before they implant.
But Dr. McCarthy has devoted his life to something else. He wants to change the reproductive workings of the adult male. He is imaginative and very capable -- the number of parallel investigations he conducts has eminent colleagues sighing with envy. He is also aggressive in pushing the envelope. Much of his work is privately funded by Catholics. He is deeply frustrated by US medical ethics restrictions, and has been reprimanded for his treatment of chimpanzees.
In parallel, there are research programs in countries with much laxer medical ethics and medical ethics enforcement. Catholic men have volunteered in large numbers. A few have contracted fatal cancers, many more have become sterile or impotent, but still they volunteer.
It seems crazy, until it makes perfect sense. Desperate times call for desperate measures. Catholics believe that every time a fertilized egg is not allowed to implant and develop into a baby, it is cold-blooded murder. These are desperate times.
So what exactly is McCarthy trying to do with the male reproductive system, and why?
"It's really quite simple. For some years now we have been able to analyze the genome of a woman's egg, and when there is a serious risk of a genetic disease, the woman may decide not to engage in intercourse at that time. This is not a sin. We cannot do this with men, because men emit millions of sperm in each ejaculation. Each one is different. They each contain half the man's genes, but which half is essentially random. Among them all, some small fraction carry genetic diseases. We do not know until the instant that a sperm penetrates the egg whether he will contribute good genes or defective genes."
"So early detection sounds like a very difficult problem."
"What we can do is to constrain the meiotic divisions during sperm formation. When we succeed, the ripening sperm are all genetically identical. To a large extent this works by killing the other sperm -- 95% of the sperm die. But the other 5% are the result of meiotic divisions that have been constrained to an exact pattern. While ordinarily the chances of two sperm cells having identical genetic structure are effectively zero, with this experimental drug cocktail tens or hundreds of thousands undergo identical meiotic division. They are numerous enough to have a high probability of causing conception -- nearly as high as an ejaculation from an untreated man."
"So you can now analyze the man's genetic contribution before intercourse too."
"Precisely! The same technology that allows us to look at the egg's structure allows us to analyze the structure of the sperm. It is actually easier. Since there are tens of thousands of identical ones, they stick out like a sore thumb in the genetic soup inside a man's testes."
"I think I see..."
Dr. McCarthy is eager to finish the story himself. "So now a couple can determine before they have intercourse the exact genetic structure of any baby that God may see fit to bless them with. There should be no need to ever abort a fertilized egg. Whatever criteria the couple may choose can be applied before intercourse happens."
"So does this mean that all a man's children would have his same contribution? That would mean he could only have all sons or all daughters, right?"
"That is correct, if it was permanent. But instead, we find that a particular meiotic constraint lasts only a few days, then it is replaced by another one. For roughly two days his genetic contribution is fixed, but then for the next two days it is also fixed, but to a different genetic structure."
"Very interesting. How is the man treated to make this happen?"
"It is easy and painless. We can give a man an implant that delivers its drugs in a consistent fashion for up to several years at a time. No doctor visits, prescription refills, or doses to forget."
"I can see that this would be of great interest to devout Catholics. But they are not the ones having abortions anyway. How could you convince other men to accept this treatment?"
"Mostly preference. A great many people are troubled by the prospect of abortion. They may go through with it anyway, but it bothers them. With this technology they would be completely free of guilt -- and mortal sin. It will also help Catholics and others who refuse to murder children to nonetheless prevent genetic defects."
"So, what stands in the way of bringing this to market?"
"There are still some issues to be worked out. Most important are the side effects. As you may know, I am collaborating with colleagues overseas where human trials have been underway for years. Before we could get approval for a US trial, we would need to greatly reduce the side effects."
"And what are these side effects?"
Dr. McCarthy gives a wily smile. "Our overseas colleagues have not been willing to share that data with us."
It is widely suspected that the overseas operations are completely controlled by McCarthy, but it's impolite to say that, and I don't want to jeopardize my relationship with him.
He has good reason to remain silent. He knows that even if the side effects are eliminated, public knowledge of what they used to be will interfere with acceptance of the treatments.
Nadine
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