Prospects in Diabetes Therapy (circa 1980)

July 27th, 2009

Download the PDF file linked at the side and you will see the first investment report on diabetes as an industry, and recommendations to investors on how to profit from diabetes. It was published twenty-nine years ago, and I wrote it.

To misquote Dave Eggars, “Prospects in Diabetes Therapy” is a heartwarming work of staggering genius. I was young, living in New York, working at a smart investment banking firm called F. Eberstadt & Co. (which, weirdly, had taken my father’s company public during the depression), and living in the delightful wide-open space of having become the first investment analyst of a new and hot industry, biotechnology. I remember my boss, Dick Emmitt, told me the company liked my initial work, and now I could pick my own topic for a report. I had been diagnosed with type 1 diabetes less then two years previous. I told him I wanted to find out the future of diabetes therapy. He liked it – no one had investigated investment opportunities in the diabetes industry – and I was given a few months to do the research.

When it was published, I became the ‘diabetes guy’ on Wall Street. It’s heady and fun to be the expert on something when you are 24. Later, when I moved to San Francisco, I owed my job to the report: Will Weinstein’s daughter had been diagnosed with type 1 diabetes and so he hired me to work at Montgomery Securities. That was my last Wall Street job. I moved toward becoming a diabetes and cell therapy entrepreneur. So in many ways this report set me on my path to where I am now.

Looking it over today, I am impressed that so little has fundamentally changed in diabetes. I also think I got a lot right in my predictions. “We believe that a biological transplant to effectively cure diabetes will be perfected between 1986 and 1994.” And remember, in 1980 there was no human insulin. Home glucose meters had been on the market less than a year. (I owned one. It plugged into the wall and took as long as a PC to warm up.)

So if you have the bandwidth to download 30MB and the time to read 51 pages, discover the future of diabetes from the viewpoint of twenty-nine years ago.

Scott's Opinion.
Follow the responses to this post through the RSS 2.0 feed.
You can leave a response.

2 Responses to “Prospects in Diabetes Therapy (circa 1980)”

1. JPMarat says:

   July 27, 2009 at 5:58 pm

   I recently read the FDA report entitled ‘Guidelines for Industry: Diabetes Mellitus 2008,’ which somehow failed to mention ‘cure’ in any of the 48 topics covered in its table of contents. The authors of the ‘Guidelines’ rather sheepishly admitted that they had not gotten around to discussing a cure for diabetes, but did note that they had included some material on preventing the development of diabetes in newly-diagnosed patients.

   I remember doing my first research work in a medical library and being very eager to cover all the articles relevant to my topic over the previous decade. But then I noticed with dismay that the only way I could tell whether the articles were from yesterday or ten years ago was by looking at the date on the cover of the journal. I started flipping back through the journals and found I could go back twenty and in some cases thirty years and still find the same topics being fruitlessly discussed, with the same debates turning forever in the same circles. I contrasted this with the situation in physics, where after a year or two of debate over some important experiment, suddenly all researchers would get the point that the existing explanatory paradigm needed to be changed or abandoned, and the science would actually grow rather than just stagnate, as is so often the case in medicine.

   In the history of diabetology, for example, it was natural for many years for researches to think that the failure of the patient to obtain nourishment from food indicated some problem with digestion rather than with metabolism. Yet the persistence of this line of thought was so stubborn that in the 1926 issue of the Yale Medical Journal the editors still published an article by someone insisting that some digestive defect was the actual cause of the disease — as though the work of Banting, Best, Collip, and MacLeod was unknown.

   Perhaps this can be excused on the theory that biology is a less precise science than physics, since many things which seem true in vitro turn out to be false in vivo, and the clarifying conceptual foundations of physics find no corresponding structures in biomedical science.

   Reply
2. JPMarat says:

   July 28, 2009 at 12:30 pm

   Approaches to disease throughout the history of medicine have typically taken the most obvious symptoms of the illness as the key to understanding and controlling the disease. Thus historical efforts to control diabetes focused on suppressing its most easily recognized and measured symptoms according to each stage of the development of medical science. Thus in the early period, when only gross and superficial examination of the patient was possible, polydypsia and polyuria were addressed by denying diabetic patients water, cachexia was sometimes addressed by feeding diabetics fatty diets, while at other times the failure to maintain weight despite adequate nutrition was addressed by starvation diets. One of the first things that a more developed medicine became capable of doing in the nineteenth century was measuring the sugar content of urine, and this made obvious a somewhat deeper, more scientifically sophisticated symptom of diabetes, its characteristic hyperglycemia. The natural response to this was to focus on suppressing hyperglycemia as the way to deal with the disease, and this fixation is now about a century old.

   But while metabolic science was already well developed by the nineteenth century and so naturally dominated the explanation of diabetes and its complications into the beginning of the twenty-first century, immunology was only taking its first steps with the work of Sir Peter Medawar in the 1940s on the rejection of skin grafts. Now, however, after about 60 years of development, immunology is just starting to move into diabetology in a significant way, and with this advance a very different set of phenomena are coming to light as possible explanatory mechanisms for diabetic complications.

   The new approach is most clearly formulated by M. Zimmerman and S.Flores, “Autoimmune-Mediated Oxidative Stress and Endothilial Dysfunction: Immplication of Accelerated Vascular Injury in Type 1 Diabetes,” Journal of Surgical Research, 155(1) 173 (2009). The authors suggest that dysregulated autoimmunity in type 1 diabetics may cause the inflammatory processes which damage both the beta cells of the pancreas initially and the vascular system later throughout the life of the patient. Zimmerman and Flores point to the anti-endothilial antibodies in the serum of patients with diabetes and suggest that targeted T-cell therapy may block the development of diabetic complications. C-reactive proteins are elevated in non-diabetic children even prior to their development of type 1 diabetes and so are independent of hyperglycemia, and these are a marker for inflammatory processes, and thus probably of autoimmunity, which can cause endothilial injury. (H. Chase, et al, “Elevated C-Reactive Protein Levels in the Development of Type 1 Diabetes,” Diabetes, 53, p. 2569 (2004)) M. Brownlee, “Biochemical and Molecular Cell Pathology of Diabetic Complications,” Nature, 414, p. 813 (2001) notes that diabetic physiology is marked by reactive oxygen species formation prior to the onset of type 1 diabetes, and that ROS could be a common mechanism for both the pancreatic beta cell damage which causes the metabolic problems of diabetes and the vascular damage which characterizes its later complications. While it is sometimes objected that both type 1 and type 2 diabetics develop similar vascular changes over time, yet only the former is characterized by autoimmunity, research now shows that in both type 1 and type 2 diabetics there is an increase of pathogenic T-cells expressing CD40 on the cell surface (as shown by increased soluble CD40 ligand in both classes of patient), and that such cells can cause both diabetes and atherosclerosis. (D. Wagner, et al, “Experimental CD40 Identifies a Unique Pathogenic T-Cell Population in Type 1 Diabetes,” Proceedings of the Academy of Sciences (US), 99, p. 3782 (2002) and F. Cipollone, et al, “Enhanced Soluble CD40 Ligand,” Diabetologia, 48, p. 1216 (2005))

   My chief concern about encapsulated porcine islet cells as a treatment for type 1 diabetics is that this may represent merely the culmination of an historical era in diabetology which is just now starting to be surpassed by immunological rather than metabolic theories of the etiology of diabetic complications.

   Reply

Leave a Reply

Click here to cancel reply.

Name (required)

Mail (will not be published) (required)

Website

CAPTCHA Code *