To a mouse.

On turning her up in her nest with the plough, November 1785.

WEE, sleekit, cow’rin, tim’rous beastie,
O, what a panic’s in thy breastie!
Thou need na start awa sae hasty,
Wi’ bickering brattle!
I wad be laith to rin an’ chase thee,
Wi’ murd’ring pattle!

I’m truly sorry man’s dominion,
Has broken nature’s social union,
An’ justifies that ill opinion,
Which makes thee startle
At me, thy poor, earth-born companion,
An’ fellow-mortal!

I doubt na, whiles, but thou may thieve;
What then? poor beastie, thou maun live!
A daimen icker in a thrave
’S a sma’ request;
I’ll get a blessin wi’ the lave,
An’ never miss’t!

Thy wee bit housie, too, in ruin!
It’s silly wa’s the win’s are strewin!
An’ naething, now, to big a new ane,
O’ foggage green!
An’ bleak December’s winds ensuin,
Baith snell an’ keen!

Thou saw the fields laid bare an’ waste,
An’ weary winter comin fast,
An’ cozie here, beneath the blast,
Thou thought to dwell—
Till crash! the cruel coulter past
Out thro’ thy cell.

That wee bit heap o’ leaves an’ stibble,
Has cost thee mony a weary nibble!
Now thou’s turn’d out, for a’ thy trouble,
But house or hald,
To thole the winter’s sleety dribble,
An’ cranreuch cauld!

But, Mousie, thou art no thy lane,
In proving foresight may be vain;
The best-laid schemes o’ mice an’ men
Gang aft agley,
An’lea’e us nought but grief an’ pain,
For promis’d joy!

Still thou art blest, compar’d wi’ me
The present only toucheth thee:
But, Och! I backward cast my e’e.
On prospects drear!
An’ forward, tho’ I canna see,
I guess an’ fear!

- Robert Burns

Other diabetic mice also cured, rub it in.

And there's this, from the New York Times, on different research toward a cure:

Three groups of scientists report today that they independently replicated a controversial finding: severely diabetic mice can recover on their own if researchers squelch an immune system attack that is causing the disease.

. . . .

"People just didn't believe it," said Dr. David Nathan, director of the diabetes center at Massachusetts General and a longtime supporter of Dr. Faustman. "People said you can't cure diabetes."

But, Dr. Nathan added, "this shows that at least in mice it has been confirmed and reconfirmed and confirmed again."

The three new papers, by researchers at the University of Chicago, Washington University in St. Louis, and Harvard's Joslin Clinic are published today in Science. In every case, the investigators followed Dr. Faustman's procedures, injecting diabetic mice with Freund's Complete Adjuvant, a mixture of water, oil and parts of dead bacteria. It overstimulates the immune system cells that are attacking the pancreas, making those white blood cells self-destruct, effectively stopping the attack and allowing the pancreas to cure itself.

The different groups calculated their cure rates in different ways but all reported that a significant proportion, though less than half of the mice, were cured. In Dr. Faustman's experiments, 67 percent of the mice were cured.

Dr. John Buse, director of the Diabetes Care Center at the University of North Carolina, urged caution.

"There are two possibilities," Dr. Buse said. "This treatment works for mice but no derivation of it will ever work for humans. Or this is the paradigm leap that is necessary to find the cure for Type 1 diabetes."

"If I was a betting person, my guess is that it probably won't work in humans," Dr. Buse added, explaining that all too often in science what works in mice does not work in people.

"Freund's Complete Adjuvant"? That sounds like some 19th-century snakeoil therapy. "Sir, have you tried my Carbolic Smoke Ball? How about a sip of Freund's Complete Adjuvant?"

Pittsburgh doctor cures type-1 diabetes in mice, makes me feel guilty.

I feel slightly guilty for my earlier intemperate comments about my four-footed friends. But why can't the mice around here make themselves useful by taking part in a clinical study, instead of just eating my peanut butter?

Anyway, this is exciting news. As you'd expect, the potential cure has some serious risks, relying as it does on some fairly precise tinkering with the immune system. To be sure, it's about time that my T cells started behaving themselves instead of attacking my beta cells in a fit of childish pique and then going to off to sulk in a corner. But while some discipline and even a little punishment might be in order (biking for 105 miles in Death Valley, maybe?), I wouldn't want to break its spirit. It still comes in handy for things like fighting colds, not to mention the occasional life-threatening infection. As the release says, the treatment may block T cells from destroying insulin-producing beta cells, but you don't want the T cells to surrender to actual threats, like France circa 1940.

Virus: Prepare for blitzkrieg!!
Immune system: [shrugs, lights cigarette]. Eh. Apres vous, monsieur. I am too much filled with the ennui.

That would be bad. Anyway, I paste the whole press release here because the science is too complicated for me to explain. More information on recruitment for the study is here, if you're interested. One of the inclusion criteria is having had type-1 diabetes for more than 5 years, so that rules me out.

Groundbreaking Human Clinical Trial for Type 1 Diabetes to Start This Spring in Pittsburgh

Researchers reverse juvenile diabetes in animal model; Phase 1 clinical trial approved by FDA

PITTSBURGH – March 27, 2006 – Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center researchers Massimo Trucco, MD, and Nick Giannoukakis, PhD, observed marked amelioration of diabetes in a mouse model by a novel treatment strategy involving specific modification of the animal’s own dendritic cells, thereby reversing diabetes in animal studies.

The U.S. Food and Drug Administration (FDA) approved the start of a clinical trial to evaluate the safety and feasibility of the treatment (Phase 1 trial). The trial is expected to begin sometime this spring and will include at least 15 patients over the age of 18, with type 1 diabetes.

Dr. Trucco, director of the Division of Immunogenetics at Children’s, and his research team will collaborate with Theresa Whiteside, PhD, scientific director at the University of Pittsburgh Cancer Institute.

Dr. Trucco and his team found that by removing dendritic cells from the blood during a two- to four-hour procedure, some 20 million dendritic cells can be harvested.

Dendritic cells are cells found in the bloodstream and normally function as one of nature’s most efficient immune function cells. The cells identify foreign substances such as cancer cells, process these foreign substances, and then jumpstart the immune response by bringing these foreign substances to the attention of T cells.

Once harvested, researchers then combine the dendritic cells with specific blockers of molecules, known as CD40, CD80 and CD86, all of which can be synthesized in a laboratory. This treatment strategy was found to inhibit the interaction and destructive effect of T cells on the insulin-producing beta cells of the pancreas, a process that is known to be a critical part of how diabetes occurs.

Subcutaneous injection of dendritic cells into the abdominal/pelvic area near the pancreas and lymph nodes, blocks the T cells as they travel to the pancreas to destroy beta cells.

“We did this in mice, giving them six injections over the course of several weeks. The injections interrupted the T cell and beta cell interaction, allowing the beta cells in the pancreas to regenerate. This enabled the pancreas of the mice to begin producing insulin again,” said Dr. Trucco, who also is the Hillman Professor of Pediatric Immunology at Children’s Hospital and a professor of Pediatrics at the University of Pittsburgh School of Medicine. “The injections proved capable of stopping this vicious cycle, and through this process curing type 1 diabetes in a mouse.”

Until now, scientists weren’t sure why the immune system attacks the beta cells, but the result is that the body stops producing insulin. When that happens, glucose builds up in the blood, but the body’s cells starve to death.

“We are very excited to begin the clinical trials and see if this process will work in patients with type 1 diabetes,” said Dr. Trucco. “A type 1 diabetes diagnosis can be devastating for children and their families. We hope this trial will have results that are life-altering for patients who suffer from this disease.”

In addition, Dr. Trucco and his team want to combine the dendritic cells with small portions (i.e. peptides) of insulin. Dr. Trucco believes that adding small doses of insulin to the dendritic cells will help guide the dendritic cells directly to the T cells. Adding the insulin ensures the dendritic cells are used specifically to block the T cell destruction of the beta cells, and not otherwise interrupt a person’s immunity. In other words, the dendritic cells are led directly to the target, the T cells that are causing the malfunction of the pancreas, and not to another part of the body.

Mice 2, Matthew 1.

Mice, I have to give you credit. First, only a few days after my trap claimed a victim, you evidently returned the favor by sending an emissary to my kitchen countertop, who proved his presence by pooping there. Nothing too elaborate -- just enough to say, in effect, "Veni, vidi, poopy." I concede that pooping in enemy territory entitles you to a point. And so the game was tied, 1-1.

Realizing that this poopage suggested that an extended campaign might be in the offing, I undertook a reconnaisance mission. I discovered that you were probably emerging from a small gap between the counter and the back of the cabinet, which allowed you to clamber onto the butcher's block that stands conveniently close to said counter. So yesterday evening, I placed a mousetrap there, baited with peanut butter as before. I left. One hour later, I returned, only to find that someone had eaten the peanut butter clean off the trigger without springing the trap.

Now, I admit, I was peeved. I baited the trap again, this time with less peanut butter, hoping to entice you into resting your tiny little paws on the trigger for better access to your meal/doom. This morning, however, you have again humiliated me by eating the peanut butter without springing the trap. Mice 2, Matthew 1.

And so evidently you have come to regard my mousetraps not as instruments of your demise, as I intended, but rather as something more like an all-you-can-eat buffet at Bob's Big Boy, or free breadsticks at the Olive Garden. Not for you will the aroma of roasted peanuts be followed by the swift descending Iron Bar of Death; no, after a quick nosh on peanut butter, you would much prefer to indulge in a delightful digestif of sacs de Ziploc, which I gather you appreciate for its fine qualities as nesting material. (Or maybe as a palate cleanser? You eat my peanut butter and then have the audacity to suggest that it leaves a bad taste in your mouth?)

Fine, mice. Whatever. But recall, if you will, this scene from Conan the Barbarian:

Mongol general: We have won again! That is good. But what is best in life?
Mongolian trainee: The open steppe, fleet horse, falcon on your wrist, wind in your hair!
Mongol general: Wrong! Conan, what is best in life?
Conan: To crush your enemies, see them driven before you, and to hear the lamentation of the women!
Mongol general: That is good.

Game on, my furry friends.

I'll have the usual.

Here is an interactive map of my usual evening ride after work. Mile markers are included. You can see that I start from work, downtown on Ross St., travel east into Squirrel Hill along the so-called "Jail Trail," east on Greenfield Ave., north along Beechwood Boulevard, before turning around at Fifth Avenue and retracing my steps (my spins? my revolutions?) back toward downtown. Then I cross the Monongahela River on the Smithfield St. bridge and head up Sycamore St.

Finally the sun is setting late enough so that I start with a little bit of daylight left, but even so unfortunately I spend most of my ride in darkness. This should change in a couple of weeks once Daylight Saving Time begins.

According to the web page, my total distance is just under 21 miles -- not perfectly accurate, since the distance is based on the multiple waypoints that I entered by hand, but close enough. I shouldn't complain, because whoever designed the page did a great job. I especially like the elevation feature. This is a great Google hack.

Rock me, Amadeus.

A few days ago, the World Affairs Council presented George Lucas with a "Global Vision Award" in San Francisco:

California congresswoman Nancy Pelosi presented Lucas his council award, likening him to renowned classical music composer Wolfgang Amadeus Mozart. The council crowned Lucas "the father of digital film" with profound insights into the globalization of culture. "Like Mozart, George Lucas is no ordinary genius," Pelosi said. "He is a magician. He will be remembered as a legend."

Yes, and the comparison is even more apt inasmuch as Mozart's "Episode I: The Papageno Menace" was virtually unwatchable, and I won't even mention the execrable "Episode III: Revenge of Die Zauberfloete."

Matthew 1, Mouse 0.

Attention, mice who may be reading this blog: You have been warned.

Help cure type-1 diabetes.

On May 6, I’m going to ride my bike 105 miles through Death Valley. My cause is the same as the last time I attempted this feat: to raise money for the Juvenile Diabetes Research Foundation. I’m asking for your help.

Forget biking through the desert: Type-1 diabetes is the ultimate test of endurance.

Sometimes, it’s hard for me to comprehend that I’ve had this disease for more than three years now. On some days, it feels like I was diagnosed yesterday. On other days, it feels like ages, and it seems as if I can barely remember a time before the myriad of strange duties that occupy me now: never leaving the house without my glucometer, checking my blood 12 times a day or more, never being far from a ready source of glucose, never forgetting the insulin pump that my life depends on.

In a way, I’m lucky. I can remember eating a simple bowl of ice cream without having to analyze its carbohydrate content. Almost all type-1 diabetics are diagnosed in childhood — a child can be in kindergarten one day and wake up in the hospital the next, as the consequences of weeks of untreated, sky-high blood sugar catch up with her. As a result, many diabetic children don’t have memories of a time like that. (Some think it’s better that way; I’m not so sure.)

Anyway, if I’ve learned anything in the past three years, it’s that living with diabetes is a marathon, not a sprint. You’re not going to prevail over diabetes alone — you just have to endure. And hope for a cure.

The JDRF’s mission.

That’s where the JDRF comes in. The JDRF is a constant source of hope for the more than 1 million Americans suffering from juvenile diabetes. It funds the research that may one day lead to a cure. Since its inception, JDRF has provided more than $680 million to diabetes research worldwide. And the JDRF is renowned for its efficient operations, spending more than 80 cents of every dollar directly on diabetes research and earning an "A" rating for efficiency from the American Institute of Philanthropy.

Recently, this has resulted in some promising developments: transplants of islet cells (which produce insulin) have meant that a few type-1 diabetics have been able to stop taking insulin via syringe or pump. Unfortunately, for the rest of their lives, the transplant recipients must take powerful drugs to suppress their immune systems (which would otherwise destroy the transplanted cells), and those drugs have their own serious risks. Still, it’s a beginning. And stem-cell research may solve this problem by allowing type-1 diabetics to grow their own, genetically compatible islet cells.

How you can help.

My goal is to raise at least $6,000 for the JDRF with my pedaling. Please help me by donating on-line at www.ride.jdrf.org/donate. It takes only a few seconds. All contributions are tax-deductible.

My dream is that a cure for diabetes will be found within my lifetime — but each day counts, for me and for the others who suffer from this disease. With your help, the JDRF can make that dream happen sooner rather than later. Thank you for supporting me and the JDRF in the fight against diabetes.

Matt McHale

Baby's first picture.

This is a first-trimester sonogram. You can see the family resemblance, I think.

Sunday's ride.

I felt good, especially considering my 40-miler yesterday -- today, I just squeaked past 50 miles, and I still had something left in the tank at the end.

Unfortunately, living on top of Mt. Washington as I do, no ride is complete without a final brutal ascent of Sycamore Street, 0.65 miles of 12% grade, with a bone-rattling chaser of Wyoming St. pave. It takes me almost six minutes, which translates to barely 7 mph.

Actually, the climb used to play a decisive role in a famous bike race, the Thrift Drug Classic, won by Lance Armstrong three times in a row. That was before his cancer, recovery, and 7-year win streak in the Tour de France. Sadly the Classic is now defunct, but in its heyday was a major fixture on the North American racing calendar. Here are some pictures from the 1997 edition that I found here.


Here's the beginning of the climb. Why is it that hills never seem as steep in photos?












And here's the pave I mentioned, which in the U.S. is called Belgium Block. There's a lot of it around Pittsburgh -- seemingly always on hills that otherwise would be quite challenging enough, thank you very much.