by Patrick Cox
December 11, 2015
If you’re like me (and most Americans), you probably added a pound or two over the Thanksgiving holiday. Moreover, the high-calorie holiday season still has weeks to run, so it seems like a good time to talk about some of the solutions to that extra fat that afflicts so many of us.
The struggle to maintain a healthy body weight is not simply a matter of aesthetics. Body fat is associated with a variety of age-related diseases such as high blood pressure and adult-onset diabetes. These conditions significantly increase the risk of heart disease, stroke, kidney failure, cancer, blindness, and a plethora of other threats to health and life.
Two-thirds of Americans are considered overweight and one-third qualify as medically obese, so it should be no surprise that the weight-loss industry is worth $20 billion per year in the US alone. The closely related fitness industry is about the same size, and despite a record of high-profile failures, the growing weight-loss drug market is well over $150 million annually.
Fortunately, unprecedented biotech advances have put the solutions to these problems within our grasp. The reason why most people don’t know about these biotechnologies is that scientific progress has outpaced government’s ability to move effective therapies into the marketplace. The good news is that more and more people are beginning to understand that the barriers keeping them from attaining better bodies as well as health are artificial.
One example of this increased awareness is the attention the new book by renowned oncologist Vincent Theodore DeVita, Jr., MD is getting. DeVita is the ex-chief of the National Cancer Institute, the innovator behind a number of important cancer treatments, and the author of numerous papers and books.
His latest book is The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable—and How We Can Get There. In it, he writes, “I’d like to be able to say that as cancer drugs have become increasingly more complex and sophisticated, the F.D.A. has as well. But it has not.” More directly, he writes, “the rate-limiting step in eradicating cancer today is not the science but the regulatory environment we work in.” [Emphasis added]
You may not want to read this book if you’re at risk for hypertension, because it’s filled with stories about the FDA impeding science and medicine… with plenty of human casualties. It will raise your blood pressure. On the other hand, if you think I exaggerate the bureaucratic control of healthcare and its cost to the American public, you should order it right now.
Though DeVita deals primarily with cancer, every area of medicine suffers from the same slow-motion institutional crawl. This applies doubly to weight-loss technologies, maybe because regulators have traditionally viewed weight loss as an aesthetic goal rather than a critical component of proactive healthcare….
Because the benefits of health accrue not only to individuals but to society as a whole via lower healthcare costs and stronger economies, we all have an interest in anti-aging, anti-obesity biotechnologies. The growing federal debt is being driven primarily by healthcare costs that rise with the average age of the population. Diabetes is one of the largest contributors to rising healthcare costs.
According to the American Diabetes Association, the disease costs more than $175 billion in direct costs annually. Add the indirect costs, and diabetes is taking more than a quarter of a trillion dollars per year out of the American economy, which is more than half of our current budget deficit. A cure for diabetes should therefore be one of our regulators’ priorities. And eventually it will be… though we’re not quite there yet.
I believe the best solution for obesity and diabetes, which I’ve written about before, is to restore the brown adipose tissue (BAT) organ that atrophies in most people as we age. Each time I cover this topic, I check the search engines to see what is top ranked. This time, I found a study published last year in the American Diabetes Association’s journal Diabetes titled, “Brown Adipose Tissue Improves Whole Body Glucose Homeostasis and Insulin Sensitivity in Humans.” This article, “Brown Fat May Protect Against Diabetes and Obesity in Humans,” provides a good overview.
Basically, the study compared men with significant brown adipose tissue (BAT) to those without. The groups were matched in terms of age and body mass index to help focus on the physiological impact of BAT. The researchers found that the “BAT men” exhibited much better insulin sensitivity, energy expenditure, and blood glucose disposal, especially when exposed to mild cold. Animal studies have also shown that BAT protects against diabetes and obesity, even when temperatures are normal, by activating when excess nutrition is consumed. People with more BAT are also more resistant to feeling cold and shivering at lower temperatures.
This raises several questions. The most obvious is how BAT tissues can be restored to prevent obesity and diabetes. Though drug companies are working on ways to activate the genes that convert white fat to brown fat, I think implanting BAT cells in the upper back (where they exist normally) is the best solution. Drugs have to be taken regularly and often activate systems other than their targets. BAT cells would permanently restore a more youthful metabolism.
A few years ago, I would have said the best way to do this would be to use a patient’s own cells, reverted to embryonic status and then engineered to become BAT cells. This is certainly possible, but gene editing technologies such as CRISPR have opened up the possibility of a superior solution.
You’ve undoubtedly picked up on the controversies surrounding CRISPR and other gene editing technologies. There are debates about the morality and dangers of using gene editing, but these arguments are really just about editing germ line cells because the gene edits would be passed down to future generations. This raises the specter of permanently altering the human species, which is the sort of thing people worry about.
Gene editing can be used for many other purposes, however, that do not involve such controversies. I believe the most important application will be in regenerative or stem cell medicine.
Creating Universal Donor Stem Cell Lines
Incredibly important stem cell therapies have been demonstrated in animals. Human trials are now on track for repairing retinal damage in the eye. One reason that the eye, like the spinal cord, is an early target for stem cell therapies is that both take place behind the blood-brain barrier (BBB).
The term is misleading since the zone inside the blood-brain barrier includes the eyes and lower spine. Regardless, the point is that under the right circumstances the immune system will not reject foreign cells inside the BBB, so immune suppression is not required for implanted cells. This enables retinal stem cell therapies for a large number of patients, utilizing a single line of cells, which keeps costs down because it isn’t necessary to create individual cell lines for each patient.
We could create individual lines of retinal stem cells by converting each patient’s adult cells to induced pluripotent stem (iPS) cells and then engineering them to become retinal stem cells. I’ve had my own cells converted to iPS cells that are identical to the embryonic cells I grew from. However, the process is time consuming and still somewhat expensive. Then, those iPS cells were engineered to become heart muscle cells, though they could have just as easily been turned into retinal stem cells. This also adds to the cost of a therapy, though for many people it would be worth it.
In fact, I’m personally in need of retinal stem cells for my right eye. Happily, I think I’ll be able to get them within a few years since several companies are now taking retinal stem cells through human trials. Because the eye is behind the BBB, the approved lines will work in most if not all patients, which will keep the cost of procedures down.
The same is not true outside the blood-brain barrier. You may have read about mice that received heart muscle stem cells repairing cardiac damage. In all those cases, donors and recipients came from the same line of mice. Mice of the same line are essentially clones and therefore have identical DNA. This prevents immune rejection when cells are transplanted from one animal to another.
Since we’re not clones with identical DNA, people needing stem cells to repair heart attack damage would need to use their own expensive iPS-derived cells or they would need to use immunosuppression to prevent rejection of the donor cells. Immunosuppression is not just expensive, it has to be kept up permanently, altering the patient’s immune system in undesirable ways. (There’s actually another solution, but it’s complicated, and I’m not going to talk about it today.)
Gene engineering, however, makes it possible that stem cell lines could be engineered so that they don’t provoke an immune response or require immunosuppression. The leading scientist in the stem cell business has mentioned this possibility publicly, and I’ll write more about this subject as information becomes available.
The Genetically Edited Stem Cell Breakthrough
It’s difficult to overstate the magnitude of the breakthrough genetically engineered universal stem cell donor lines would represent. We could see the creation of off-the-shelf universal cell lines for a wide variety of uses outside the BBB. Non-immunogenic stem cells could be given to any heart attack victim to repair damaged heart muscle cells immediately after a myocardial infarction. Many other organs in need of repair, such as the pancreas or liver, could also be cheaply treated.
Universal donor BAT cells would be a no-brainer, lowering the cost of such a therapy to that of a minor cosmetic surgery, like those performed to fill in the age-related hollows (lipoatrophy) under the eyes. If, as the literature indicates, this significantly addresses the problems of diabetes and obesity, the benefit to the economy and healthcare system would be immense. It could, in fact, balance the US budget.
Clearly, this therapy is not yet available, but it could be quite soon, because of Japan’s regulatory reforms. The problem now is financial, and I admit that I’ve been unsuccessful in my efforts to attract someone with deep pockets to this challenge. This is always the way it is with new technologies, though. Most investors don’t recognize the promise and financial potential of radical innovation until somebody else brings it to market. Then the herd jumps in after the big profits are already taken.
Next week, by the way, I’ll talk about new research indicating that we can improve BAT organ function via non-drug and non-surgical means. I don’t believe these techniques will work nearly as well as BAT transplants, but it could give you an edge in the battle against obesity, hypertension, and diabetes. I’ll also show you research indicating that nitrate-rich food sources may be a better solution to hypertension than existing blood pressure meds.
— Gene Editing Could Simply and Cheaply Solve Obesity and Diabetes was originally published in a slightly longer form at Transformational Technologies.