At the turn of the century, while awaiting the completion of the Human Genome Project (HGP), scientists organized an informal sweepstake for researchers to guess the number of genes in the human genome. Early guesses of 100,000 in the early 1990s crept down closer to 50,000 later in the decade. In the end, a much smaller number claimed victory: 25,947, which was closest to the then estimate of 24,500.¹ However, 21 years later, the count is still ongoing. 

     

With the sequence in hand, a bigger question emerged: what's a gene? Around the HGP era, many scientists defined a gene as any region of the genome that encodes a protein, and gradually converged on the number of protein-coding genes.² But according to other definitions of a gene, the count doesn’t end there. “On top of the 20,000 protein-coding genes, we have another 15,000 or 20,000 noncoding genes,” said Steven Salzberg, a computational biologist at Johns Hopkins University. 

Salzberg noted that many of those might not turn out to be genes under another definition of a gene, which is any section of the genome that produces a protein or RNA that the body uses, thus incorporating functionality into the definition.^2,4 “We only know the functions for less than 5% of them, so they might just be noise,” said Salzberg. 

Scientists still don’t know the exact number, but Salzberg is optimistic that new technologies will help refine the gene catalog. For him, this is more than a counting exercise. Medical research and practice rely on a detailed catalog of human genes. “If there's a gene that's not annotated, it's not known. They won't look at it,” said Salzberg. “We'd like to be able to reassure them [that] all the genes are known.”

Pregnancy is a time of massive physiological upheaval that disturbs every major organ system in the body. “We’re often told, ‘don’t worry, it all resolves afterwards,’” said Liisa Galea, a behavioral neuroendocrinologist at the Center for Addiction and Mental Health. “But does it really? Or is there a long-lasting signature? I’ve always been fascinated by that.”

     

In a new study in rodents, Galea identified some of these signatures of motherhood in the brain, describing persistent differences in markers of neuroinflammation and plasticity.¹

In humans, research suggests that male and female brains age differently in the context of both health and neurodegenerative disease, but the mechanisms underlying these complex sex differences are not fully understood.^2,3 “We need to understand what kind of female-specific experiences might be driving increased risk or resilience,” said Galea.

To begin unraveling this mystery, Galea and her team examined cellular and molecular differences in the hippocampi of rats with zero, one, or two litters of pups.¹ They found that rats with one or two litters had higher levels of post-synaptic density 95 protein—which plays a key role in the ability of neurons to alter their connections with each other—compared to non-mothers, both shortly after giving birth and in middle age. While rats without pups experienced a decline in neural stem cells with age, mothers had similar neural stem cell densities at both time points. In middle age, rats with two litters had greater densities of microglia, the brain’s immune cells, compared to rats without pups.

“I found the conclusions to be insightful,” said Jessica Bradshaw, who studies maternal brain health at the University of North Texas Health Science Center and was not involved in the study. “This highlights that even a healthy pregnancy can have short-term and long-term effects on the brain.”

In the late 2000s, as a graduate student in Michelle Hasting’s laboratory at Rosalind Franklin University of Medicine and Science, I worked on targeting RNA splicing for disease therapy using radioactive isotopes to detect RNA expression. 

         

One winter afternoon, our laboratory manager and I tried to raise the frigid temperature in the lab to a balmy 60 degrees Fahrenheit. Suddenly, a pipe burst above the door that was the only exit to the room. Hot water shot across the doorframe and straight into a container with liquid radioactive waste. 

At the time, we used phosphorous 32 (P-32), an isotope with relatively low levels of radioactivity and a short half-life in our experiments. Although we can work with P-32 for hours with minimal risk, we wanted to avoid any unnecessary exposure. 

As we watched the radioactive waste overflow onto the floor, we quickly climbed onto the lab benches and called for help. I’d never dealt with a spill quite like this, but we stayed composed, well prepared from our lab safety training. Once maintenance shut off the water, we went to work with the detailed clean up procedure.

We wiped up all the water and spritzed Fantastik, a handy household cleaner that removes isotopes. Then we used a Geiger counter and a scintillation counter to confirm that there was no residual isotope.

Later, we discovered that a fire had occurred in the lab many years prior, and the construction company repaired the damage. However, the company never replaced the insulation in the ceiling, which left a risk to the pipes. Thankfully, they replaced the insulation after this incident. 

It was a close call and a reminder to stay vigilant about lab safety. We never know when a burst pipe will test the importance of proper lab safety practices! The incident could have been much worse if we had neglected lab protocol and overfilled the waste container.

This interview has been edited for length and clarity.