Author Archives: Mike White

The Genetic Nightmare of Diabetes

After 10 years of genomic studies, our understanding of the genetic architecture of diabetes is… still a mess. Or, if you prefer, a nightmare. That’s the message of the most extensive Type 2 Diabetes GWAS to date. Looking for rare genetic variants linked with diabetes, researchers performed whole-genome or exome sequencing on 15,000 people… and came up with nothing new.

This is an important negative result, in that it advances our knowledge of the genetic architecture of diabetes – odds are that many common genetic variants, each with individual small effects, contribute to one’s total genetic risk for the disease. It also illustrates just how hard it will be to realize the goals of personalized medicine. So let’s avoid the hype when we talk about how genomics is going to revolutionize medicine.

I explain the study and its implications in my piece this week at Pacific Standard.  Go read it to learn more about the challenges ahead that face personalized medicine.

Apocalypse 1913: Adrift In A Hostile Cosmos

Arthur Conan Doyle’s The Poison Belt (1913)

415px-Strandus-1913-05End of the world narratives are typically about a fight for survival – people fight for food, shelter, and safety as the asteroid, pandemic plague, or zombie hordes threaten to wipe out human life. This was just as true of SF a century ago as it is today: In 1912, Jack London’s The Scarlet Plague featured armed Berkeley professors, holed up in the chemistry building as a plague swept away civilization; while Garrett Serviss’ The Second Deluge tells of a thousand lucky survivors who, in a modern ark, escape a world-wide flood.

The next year, Arthur Conan Doyle also published a novel about a group of hardy survivors. But the terms of survival in The Poison Belt are much more ironic: Professor Challenger and his fellow adventurers, who had fought off dinosaurs and ape-men on a remote South American plateau in Doyle’s 1912 The Lost World, now confront the extinction of human life as passive observers, watching the destruction of humanity from the window of the “charmingly feminine sitting room” of Professor Challenger’s wife. Continue reading

Off-the-shelf drugs against Zika

As with the ebola outbreak on 2014, we’re facing the Zika pandemic without any drugs or vaccines.  Several rapidly developed Zika vaccines are now entering clinical trial, but we urgently need effective drugs that we can give to infected pregnant women, to protect their unborn children from the awful birth defects that the virus can cause.

Drug development takes a long time. However, one group at the University of Texas Galveston tried a short-cut: test drugs that are already approved by the FDA to see if any can prevent Zika infections. They tested 700 drugs in vitro (i.e., i cells in a petri dish) and found 20 that showed some efficacy in different cell types. Some of these are safe to give to pregnant women, and at least one, ivernectin is a cheap anti-parasite drug already taken by millions of people world-wide.

Obviously whether any of these drugs are effective in actual people is an open question. But the beauty of this is that the safety of these drugs has already been tested. We can start enrolling people in clinical trials to test their efficacy now.

I wrote more about this story over at Pacific Standard – go give it a read.

The Legacy of Slavery in African American DNA

This week at Pacific Standard,  I discuss a recent study that examines the influence of slavery and its discriminatory aftermath in the genetic diversity in over 4,000 African American genomes. One of the most striking results of the study is probably the most obvious: On average, about 15% of the DNA of African Americans is of European origin – and, according the researchers’ best statistical model, that European DNA largely dates back to before the Civil War. That was a time when interracial sexual relations overwhelmingly took the form of whites raping black slaves. After the Civil War, according to the model, admixture between blacks and whites dropped off sharply.

Like I said, it’s not particularly surprising, but the breadth of the genetic legacy of slavery is striking.

The study makes some other intriguing suggestions about African American genetic history, especially regarding the enormous demographic shift of the Great Migration (~1915-1970), when 6 million African Americans left the South and settled in other parts of the country. The big takeaway from this study is that African American genetic history is one of coercion: coerced migration and coerced sex over a relatively short period of time, which left strong signals in the genetic diversity of present day African Americans.

Aside from the historical aspect, studies like this matter if African Americans are going to participate in the ongoing development of personalized genomic medicine. Because the genetic structure of the African American population differs from that of whites, African Americans have different genetic risk factors for disease – and even different risk variants for the same diseases. Studies like this lay the groundwork for an inclusive practice of genomic medicine.

Sunday Science Poem: Darwin and Happy Endings

Wisława Szymborska’s “Consolation” (2002)
henri_rousseau_-_fight_between_a_tiger_and_a_buffaloEvolution has always been more controversial socially than scientifically. After Darwin published the Origin, the idea that all species descended from common ancestors was quickly accepted by most biologists (though his proposed mechanism of evolution, natural selection, remained controversial until the 20th century). Socially, however, evolution was and remains difficult for many people to swallow. The literalist beliefs of religious fundamentalists of course conflict with evolution. But even among those who don’t have a particular religious axe to grind, discomfort is not uncommon. Evolution in practice is brutal: we posses our unique adaptations – our brains, our opposable thumbs, our ability to talk, to socialize, to feel, see, and touch – thanks to the selective death of billions of organism over eons.

In her hilarious poem “Consolation”, the late Nobel-winning Polish poet Wisława Szymborska ironically contrasts the brutality of the real world in which evolution plays out, with the romantic world we construct for ourselves. She portrays Darwin, the great thinker who first grasped the harsh reality of evolution, as someone who escapes by reading novels with only happy endings.
Consolation

Darwin.
Supposedly for relaxation he read novels.
But he had a requirement:
they couldn't end sadly.
If he happened on one,
he flung it furiously in the fire.

True or not –
I gladly believe it.

Roaming in his mind over so many times and places
looking back on all the extinct species,
such triumphs of strong over weak,
so many tests of survival,
sooner or later all in vain,
that at least in fiction
and its micro-scale
he had a right to expect a happy ending.

And so necessarily: sunrays behind a cloud,
lovers together again, kin reconciled,
doubts dissolved, faith rewarded,
fortunes recovered, treasures dug up,
neighbors regret their mulishness,
good names restored, greed put to shame,
old maids married to respectable ministers,
schemers expelled to the other hemisphere,
forgers of documents cast down the stairs,
seducers of virgins hurrying to altars
orphans taken in, widows embraced,
pride humbled, wounds mended,
prodigal sons invited to the table,
the cup of bitterness poured into the sea,
tissues wet with tears of reconciliation,
universal singing and music-making,
and the puppy Fido,
lost already in the first chapter,
let him run home again
and bark joyfully.

Translation from the Polish by Michael A. White (2016)
Image: “Fight Between a Tiger and a Buffalo”, Henri Rousseau (1908), via Wikimedia Commons.