a discourse on sugar and youth decay

Construction Bridge Wall Painting on Mass Ave by Kendall/MIT

Recently, I was lucky to be invited to an event where I heard Professor Douglas Melton of Harvard University's Department of Stem Cell and Regenerative Biology speak about his most recent work in stem cell research. Professor Melton's lab focuses on the pancreas and specifically on development of cells within this vital regulatory gland. His talk had two parts, the first on the pancreas and the second on a quest for the fountain of youth.

Pancreas

The former part of his talk brought me all the way back to my formative years in science, before I ever even knew about the monetary aspects of pharmaceutical/healthcare investing. In my sophomore year of college, I took a physiology class, during which I participated in an interesting lab exercise to study the metabolism of mice through their excretions. The mice were split into different groups, then given protein-heavy, carbohydrate-heavy, and fat-heavy meals, and we studied their urine and poop levels for 36 hours straight. (Yes, we did indeed have to wake up every 3 hours in the middle of the night to trek down to the medical school lab to analyze rodent turds...)

Through that experiment, I gleaned lessons on the different metabolic pathways of different foods. Protein is not broken down until it reaches the stomach, where pepsin cleaves the large molecules down into single amino acids. Fat, similarly, is broken down by lipase, into smaller moieties. Carbohydrates begin their metabolism in saliva, where amylase cuts the complex carbs into increasing simpler pieces as it is transported through the esophagus and into the stomach. The pancreas kicks in to regulate the amount of this broken-down simple carb - glucose - in the bloodstream.

The pancreas does not receive the recognition it deserves. I personally never gave it much thought until Prof. Melton's talk. Nested posterior to the stomach, which growls a reminder every few hours to fill it, and beneath the heart, whose beat is routinely monitored by athletes and physicians alike, the pancreas' part in sustaining bodily continuity is largely overshadowed by its noisy neighbors. But truthfully, the pancreas, a regulator of carbs in the body, is a very important player in the grand scheme of staying alive. Indeed, the pancreas' endocrine and exocrine cells secrete various important messengers to not only regulate (increase or decrease) the glucose level of blood, but to also regulate its own function.

The particular type of pancreatic cell that Prof. Melton focused on in his talk are beta cells, which secrete the hormone insulin. Insulin production and release is triggered by a carbohydrate-happy feast, and its presence in the bloodstream causes a decline in the level of glucose, which is the end product after carbohydrates have been broken down by amylase in the saliva and stomach. Beta cells are particularly susceptible to disease -- specifically diabetes I and II -- which are conditions in which an individual can no longer keep blood sugar to a safe level.

Though we don't give much thought to the oblong gland that is affected by it until it is affected, diabetes mellitus is a fairly familiar disease. Anyone who has ever stayed home from work/school and indulged in daytime television is probably at least familiar with it through Wilford Brimley's (now oft meme-ified) advertisement for Liberty diabetic medical supply. On the other end of the age spectrum in pop culture, many celebrities deal with this harsh illness, including the youngest Jonas Brother, Nick. And of course, unfortunately many of us have loved ones who suffer from diabetes.

While there are various types of diabetes, they share the distinctive feature of a lack of or deficiency of beta cells. The cells are either destroyed by the body through auto-immunological processes (Type I or "junvenile" diabetes) or rendered less efficacious (this seems to be the theory behind Type II or "adult onset" diabetes). I'd come to know of it as "tang-niao-bing" from an early age, which literally translates into "sugar-urine-disease."

Prof.  Melton described some exciting work where they have been able to influence stem cells, which are omnipotent and can develop into anything, to turn into beta cells. In the past, diabetes has become manageable because the brilliant scientists of earlier generations were able to create the life-critical peptide digestive hormone by purifying animal-sourced insulin, and then by genetically engineering Escherichia Coli, rod-shaped little guys that have pretty much become the fruit-fly of bacterium labs, to turn into insulin-synthesizing factories.

Our scientific forefathers have allowed us to turn this once-deadly disease into a more manageable illness.
But there are still a host of problems, including

• Regulation of amount of insulin. While our pancreases are amazingly self-regulating, injection of external insulin may be too high or too low.
• Accessibility/inconvenience. Equipment is needed to inject insulin, and that means one needs to worry about makign accommodations.
• Needles and finger pricks. To measure blood sugar and inject insulin. A far cry from a fun time.

Insulin injection has seen some evolution. There are now small portable pumps that do the job and reduces the need for a diabetic to constantly be pulling out syringes. But it is, after all, still a very artificial process.

But what about replacing the damaged beta cells so that the gland can again produce its own insulin? That's what Prof. Melton's research team is focused on. They are developing beta cells to be implanted directly into people whose own beta cells have been destroyed - through disease, life style choices, or autoimmune processes.

I think that his research can have wide-reaching effects. Diabetes is not the only disease that can be brought on by autoimmune reactions. Arthritis, psoriasis, Celiac disease, and multiple sclerosis are among some of the other ones that plague citizens of the world today. If Prof. Melton's Petri dishes can beget beta cells, then maybe they can forge from stem cells some of the other life-sustaining cells that are destroyed by auto-immunological processes. The implications of that not only piques my scientific interest, but touches me on a very personal level. I am excited to see Prof. Melton's team succeed.

Fountain of Youth

Next, Prof. Melton talked about a really cool experiment he did ... also with mice. Fortunately for him, poop measuring was not part of the protocol. In a quite clever mechanism to study age, he sewed two mice together -- one young and one old.

Yes, needle and thread.

Sounds cruel, but according to Prof. Melton,
"Believe me, these mice did not mind being sewed together, they went about their daily activities just as before. It helped that they lived in the mouse-equivalent of the Ritz Carlton, where they got all the food and sex they wanted."

Indeed. That's only fair, right?

Attached to one another like bananas to a bunch, the furry duo shared a blood stream at their point of conjunction. Prof. Melton's team was interested in seeing whether it was "old" factors in the aged mouse was what caused the vitality and youth of a mouse -- of any mammal -- to decline over time. That is, is it years of breathing pollution, and partaking of other vices -- smoking, drinking, gluttony -- that build up and cause us to lose our ability to spring up, unfettered from falling off our bikes and feel nearly no pain the day after?

Or is it was the "youth" factors in the young mouse that allowed such younger individuals to repair bodily damage more quickly and be more resilient to disease? Luckily for us, the Melton lab found that it was the latter. The older mouse sewn to his younger companion was able to repair damaged muscle and bone more quickly than the same old-aged mouse without the conjoinment of a young mouse.

Senescence, then, is potentially something we can control. If we can isolate the youth factors in young people's blood and recreate those factors (because after all, it is the decay of these youth factors that diminishes our youthfulness over time) or use stem cells to make cells that may do so in-vivo (like the beta cells), then we may be able to make aging a more graceful and less painful, tiresome process.

These implications of Professor Melton's talk left me in a state of excitement. My heart was beating out of my chest as I walked across the Mass Ave bridge that connected the Harvard Club (where the talk was held) and MIT, and thought that this city, where so many top-notch scholars are at work, could be the very place that solves aging. As a former research assistant, I can appreciate the hard work and dedication that it takes to hypothesize and test a concept. As a current investment professional, supporting the allocation of capital in places like pharmaceutical development, I can also understand the long road from concept to practicality. One thing I know for sure, though, is that only great things can come out of a marriage of brilliant minds and patient capital, and I want to.... no, I *WILL* .. be part of that.

Links:
(1) Prof. Melton's Harvard Home Page
(2) Science Magazine Article on the Fountain of Youth