Liz Blackburn, the 2009 Nobel Prize Winner in Medicine or Physiology

I have been running a science book club (DtaS book club) for the past couple years. Last month, we read our first biography, that of Liz Blackburn, the 2009 Nobel Laureate in Medicine from UCSF. The book, available freely online via Google Books, recounts Liz's meteoric rise in the scientific community, essentially birthing the study of telomeres – the end caps of chromosomes. Her work revolved around greater understanding of telomerase, the enzyme which is involved in the lengthening and shortening of these end caps. The process is complicated and not fully understood, but the basic (and oversimplified) idea is that as cells divide – the ends of chromosomes shorten leading to their eventual death. Telomerase helps repair and lengthen these end pieces of DNA, affecting the life span of cells. This has implications in aging, cancer research, even correlations to quality of life. Liz came off as the heroine in this tale – she played the role of the curious scientist that fully committed to understanding the role of a specific biological system. Alongside a small group, Liz pioneered study in this area, leading to an explosion of research in this field.

The tale of her scientific discovery is riveting, but nearly as fascinating as her personal tale. Liz is the only the 8th woman to win the Nobel Prize, indicative of the gender gap in scientific research. I was personally struck by a particular comment in the book: At 38, Liz had become a full professor at UC Berkeley and attained great respect within the field – she had finally "achieved enough to have a child". This struggle is oft-discussed and debated within the science world, but I was absolutely struck by the brutal honesty of Liz's quote.

Even though Liz is widely seen as one of the most polite and thoughtful scientists you'll ever meet, she has found herself in the midst of many controversies. One in particular lead to great deal of fame, her widely publicized dismissal from President George W. Bush's Council on Bioethics in 2004. This council was charged with making recommendations on policy surrounding embryonic stem cell research, but was often criticized by the scientific community for advancing the political agenda of the administration. Liz details her side of the story in an editorial to the New England Journal of Medicine, citing her frequent disputes with the chairman of the council, whom she accused of ignoring comments and input from the scientist council members.

Liz will be in conversation with Susan Desmond-Hellman, the current Chancellor of UCSF, at the Commonwealth Club. Sue is certainly no stranger to this conversation – she is widely considered one of the foremost experts on cancer research today. Sue was formerly president of product development at Genentech and was involved the development of Herceptin and Avastin – two of the most effective cancer drugs on the market today.

Liz Blackburn: A Life in Science
When: Wednesday, August 4th 530-730 PM
Where: Commonwealth Club, San Francisco
Cost: $20 General, $12 Members, $7 Students
Details: On October 5, 2009, UCSF molecular biologist Blackburn learned that she had received the 2009 Nobel Prize in Physiology or Medicine, for her co-discovery of an enzyme that plays a key role in aging and cancer. Blackburn discusses a life in science. We encourage both scientists and non-scientists to come hear her reflections on an unfettered childhood, skirting the 'safe' scientific projects, the benefits of not listening to naysayers, and the difference between good and bad stress.

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Mole voles do fine with one X and no Y
chromosome.

Last blog I talked about the Transcaucasian mole vole. This little burrowing mammal has lost its Y chromosome over time. Now both males and females have only a single X.

I focused on how scientists can't yet figure out how there are any male mole voles running around. This week, I want to focus on what this means from an evolutionary perspective.

These little animals show that massive changes in chromosome structure can be tolerated and the species can do quite well. Even when the chromosomal change results in a significant increase in miscarriages.

About half of a mole vole's fertilized eggs don't survive to term. Why not? Because these embryos have either no or two copies of the X chromosome.

Most mammals have two copies of each of their chromosomes– one from mom and one from dad. At the end of meiosis, each chromosome copy ends up in a different sperm or egg. This is so that when an egg and a sperm combine, the new mammal has the right number of chromosomes.

Mole voles end up with half of their sperm or eggs with one X chromosome and the other half with no X chromosome. There is a 1 in 4 chance that a sperm without an X chromosome will fertilize an egg without an X chromosome. Since mammals need an X chromosome to survive, these fertilized eggs don’t make it to term.

There is also a 1 in 4 chance that a sperm with an X chromosome will fertilize an egg with an X chromosome. In most mammals, this would be OK– the fertilized egg would go on to become a female.

But this is fatal for mole voles. Most likely this is because these animals have a defective Xist gene. This gene's job is to keep only one X chromosome on in any cell.

Whatever the reason, these mole voles deal fine with the fact that half their fertilized eggs do not make it to term. This means that chromosomal rearrangements and changes that affect fertility can be tolerated. At least in the mole vole.

This is important because one of the key differences between a chimpanzee and a human at the chromosome level is that humans have 46 chromosomes and chimpanzees have 48. Looking at the DNA we see that human chromosome 2 looks just like chimpanzee chromosomes 12 and 13 fused together.

Some people argue that this sort of rearrangement wouldn't be successful because at an early transition stage from 48 to 46 chromosomes, half the fertilized eggs would not make it to term. These fertilized eggs would either be missing or have an extra chromosome. Just like the mole vole.

Here we have a mammalian example where this isn't an issue. This little mole vole is doing quite fine thank you very much. As our ancestors most likely did too.

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Transcaucasian mole vole. Image Courtesy of Heike HimmelreichOne of my favorites is a little burrowing mammal called a Transcaucasian mole vole. These guys live in the Caucasus Mountains of Armenia, Iran, Turkey, and Azerbaijan. There they are born, live, have babies and die. All without a Y chromosome.

This is really bizarre. In most mammals, two X chromosomes usually means that the animal is female and an X and a Y means the animal is male. All mole voles have a single X chromosome. So technically, there shouldn’t be any males running around. And yet, clearly, there are.

So what distinguishes a boy mole vole from a girl mole vole genetically? No one really knows.

In most mammals, the Y chromosome causes a fertilized egg to turn into a male because of the SRY gene. This gene starts a cascade of events that eventually results in a male.

One possibility would be if the SRY gene happened to move to another chromosome. There are certainly cases of this happening even in humans.

If this were the case, then maybe a different chromosome has the SRY gene in mole voles. Maybe there are versions of the gene that work and versions that don't. Now we have a gene no different than an eye or hair color gene.

Good model but it isn't true. Scientists have looked but it appears that these little guys don't have an SRY gene. They make the male/female decision in a completely different way.

Most likely somewhere along the way a gene mutated so that it could now determine the sex of these mammals. When this happened, the loss of the Y didn't matter much and so it was lost. The mole vole evolved into a Y-less mammal.

Of course, if any chromosome had to go it would be the Y. It has been under constant attack ever since it distinguished itself from the X chromosome 200 or 300 million years ago. It has gone from being one of the biggest chromosomes with 900-1400 genes to a bit of DNA with around 80 genes.

There are even active discussions about whether the Y is on a death spiral in all mammals. Soon we may all be mole voles. Or be gone. Some of my recent posts elsewhere on this topic:

Males going extinct?
Fish that change gender

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