Genome-edited people

In the near future, we may talk about a “genome-edited person,” a phrase that I picked up at the Stem Cell Meeting on the Mesa last week.  This idea was raised around experiments showing that it’s possible to engineer hematopoietic stem cells to resist HIV infection and essentially eradicate the virus from an infected individual (a mouse, in this case).  These experiments spring from a bone marrow transplant that was done in an HIV-positive patient with acute myelogenous leukemia.  The patient received bone marrow from a donor with a rare mutation that makes his T-cells resistant to HIV infection.  So far, the patient is HIV- and cancer-free.  Through genome editing, that same mutation could be introduced into a patient’s hematopoietic stem cells and reintroduced into their bone marrow.

Six years ago, Shinya Yamanaka discovered that just four transcription factors are needed to reprogram a cell whose fate was sealed into a stem cell.  This year, he shared the Nobel Prize in Physiology or Medicine for his contribution to regenerative medicine.  This technology is a like a science fiction dream come true.  We can take someone’s skin cells or fat cells and turn them into any other cell in the body- neurons, blood, heart cells that beat.  If people have a genetic disorder, this could be corrected through genome editing of stem cells we create from their body.  This technology will change medicine, but it’s still in its infancy.  This was a common theme of several talks: the science isn’t perfect.

More researchers are studying iPS cells at the same time that we are improving our ability to accurately sequence the entire genome and epigenome.  Turns out, reprogramming introduces small changes, some of which may be significant. Gene activity changes because DNA methylation states change.  Mutations are introduced by retrotransposons (sometimes called “jumping genes”), pieces of DNA that move around and can jump back into the genome at the wrong spot.  So the DNA is the same, but not.  A bump in the road that’s sure to be understood or overcome with time.

The California Institute for Regenerative Medicine (CIRM), which was founded by a state ballot measure to fund and direct stem cell research in the state, manages the larger picture of stem cell research and related translational medicine in the state.  Part of their plan includes stem cell banking and developing Genomic Centers of Excellence.  Together, these will help us better understand the genetics, genomics, and epigenetics of stem cells.  For now, the field is aware that reprogramming has unintended consequences. It’s important that the public is aware of this, too.  Patients and patient-advocates are very eager to see this technology available clinically, but scientists want to make sure that we’re not unintentionally hurting people by using it.  Once the technology is sorted out, both stem cell therapy and genome editing may become commonplace.

Too much of a good thing

Kids are getting 7-15% of their total energy from sweetened drinks.  The beverage industry claims that this is small potatoes.  “Focusing on a small source of calories rather than on the total diet is a misplaced allocation of resources,” according to the American Beverage Association, quoted in the LA times.  But is it really a small source of calories?

Three studies published last week in The New England Journal of Medicine indicate the answer is “no.”  In two of the papers, researchers subbed zero-calorie drinks for sweetened drinks.  The de Ruyter study was especially well controlled: they made the drinks to look and taste identical, the drinks were given out in school and most kids drank them over their morning break. Also, they collected urine from the participants to confirm compliance.  The take-home message?  Kids who drink sugary drinks are fatter and have a higher BMI.

The third paper looked at adults (gulp!) and found that if you are genetically predisposed to obesity, then drinking sweet beverages in an extra-risky proposition.  They screened people for common genetic variations (SNPs) that are associated with high BMI.  For those folks, one sugary drink a day is much more likely to tip the scales to overweight or obese than for people who have “skinny” genes.

A pound of weight gain comes from consuming 3500 more calories than you need.  Lots of kids drink 300 calories worth of sugary drinks every day.   Unless they are scaling back the food they eat by 300 calories, those drinks add up to an extra 2 pounds per month, or 24 pounds per year.  Follow the math, and it equals an obesity epidemic.

It’s unrealistic to think that kids will only drink thirst-quenching water and satiety-inducing milk.  My grandmother’s advice rings truer than ever today: “too much of a good thing is not a good thing.”