The Six-Point Inspection, offer readers with very helpful capsule summaries and reviews of science and technology books exploring complex and nuanced ideas. For those of us who like to knock one back every so often, they also helpfully provide “cocktail fodder” that you can take away from books and bring to your fellow revelers.
For People, Parasites, and Plowshares: Learning From Our Body’s Most Terrifying Invaders by Dickson D. Despommier, the reviewer suggests Despommier’s recounting of how Yul Brenner sued Trader Vic’s at the Plaza Hotel after contracting trichinosis there in 1973 as possible cocktail fodder. Brenner won a settlement of $125,000 but it’s possible the parasite slowed down the growth of the lung cancer that killed him 12 years later.
Here is the excerpt from the book in which Despommier discusses how the parasite might have prolonged Brenner’s life. Despommier goes on to explain some of the science and medical research behind Brenner’s experience:
The following anecdote could be scripted right out of a Hollywood melodrama, but it is true nonetheless. You may be familiar with the renowned actor Yul Brynner. He starred on Broadway in The King and I. In film Brynner was equally well-known, with featured roles in The Ten Commandments, Taras Bulba, The Magnificent Seven, and Westworld, to name a few of his more popular ones. In 1973 Brynner and three dining companions all contracted trichinellosis at a popular restaurant, Trader Vic’s, located in the posh Plaza Hotel in New York. A year later he won a settlement of $125,000 in damages. If he knew that the infection might have been responsible for prolonging his life, even a little, he might have thought twice about the litigation. Tragically, Yul was also a heavy smoker and was diagnosed with lung cancer. He died several years later from it on October 10, 1985. I think that it is quite possible that his trichinella infection slowed down the growth of the cancer, since this worm is known to activate all aspects of our immune system, except those responses that might act directly against the Nurse cell. Data from laboratory animal experiments using a wide variety of other maladies plus infection with trichinella strongly support this view. Tumors of certain kinds regress, and many infectious agents that would ordinarily make a host sick do not cause disease in those infected with trichinella. BCG vaccine (a killed preparation of the bacillus of Calumet and Guerin, a TB-like microbe) has similar effects on our immune system, placing all aspects of it on a higher level of alert surveillance for things like cancer cells and pathogenic micro organisms.
Trichinella offers us other clues that could be of value. For example, the parasite may provide a new approach to the treatment of type 1 diabetes. In this insidious illness, the patient’s pancreatic islet cells fail to continue the production of insulin. The reasons for this are poorly understood, but one viable hypothesis suggests that sometime in our childhood, we encounter a viral infection whose antigenic signature closely resembles that of the islet cells of our pancreas. When we fight off the virus, we are left with an immune system that now turns its attention to our own tissues, since the infectious agent is no longer present. This kind of disease is referred to as autoimmune. Standard treatment for juvenile diabetes involves frequent injections of insulin. Failure to do so has dire consequences. But, unfortunately, the treatment is not perfect, even when the patient is diligent. Eventually small excesses of sugar in the blood stimulate the formation of unwanted new capillaries. When the heart is unable to ef.ciently pump blood to all parts of the body because of the extra vasculature, the peripheral circulation begins to fail. The loss of fingers and toes may occur, followed by renal failure and loss of sight. Eventually death ensues. This dire prognosis means that other treatment approaches are desperately needed.
Transplanting pig islet cells into diabetic patients is one treatment that has been pursued, and it seems like a viable alternative if certain issues could be addressed. Early human clinical trials with this treatment were promising but quickly encountered several hurdles. The first was, of course, the fact that a pig donated the cells. Most of the time our immune system is really good at distinguishing between us and everything else, so immunosuppression of the recipient is necessary. The second hurdle proved far more dif.cult to jump over. When individual islet cells were injected intravenously, they became stuck in the patient’s capillaries, just like the newborn larvae of T. spiralis did during their migration in the bloodstream. Oxygen levels dropped in the affected area, triggering the synthesis of a new section of capillary that bypassed the blockage of the circulation at that point, restoring blood flow. This left the islet cells stuck on the tissue side of the circulatory system surrounded by nonleaky vessels, so when blood glucose levels went up after the patient ingested a meal, the islet cells were slow to respond. Without a mechanism for rapidly getting insulin into the bloodstream, the endothelial cells that form the capillaries in all the tissues ate up the excess sugar and multiplied, creating a tangle of new vessels. In the end, islet cell transplants slowed down the overall pathology of type 1 diabetes, but the disease eventually won out and the patients returned to an acute state of illness.
How can a worm that lives a long time in a portion of an altered muscle cell help these diabetic patients? Recall that trichinella induces sinusoids during Nurse cell formation, and that these vessels are associated with the endocrine gland system because they allow hormones easy access to the venous circulation. What if we were to learn that trichinella induces its sinusoids by secreting a speci.c protein that, in the infected host, initiates the metabolic program that generates that particular type of vessel? Using a molecular biological strategy, we could then search the worm’s genome for the gene encoding our desired protein and clone it into pig embryos. By connecting a molecular on-off switch, known as an inducible promoter, to that gene so we can control its expression, we could then let these special pigs grow up.
Whenever we desired, we could isolate their pig pancreatic islet cells and inject those engineered cells into our patients. Instead of eliciting capillaries, we could turn on the switch for the trichinella gene responsible for making sinusoidal vessels. Now the insulin hormone molecule can easily traverse the vessel wall and rapidly enter the venous return. We would still need to mildly immunosuppress the patient, but now they could function on their own without the need for injecting insulin.
We may be a long way from this achievement, but because we have determined the entire DNA sequence of trichinella’s genome, anything seems possible. The first step would be to identify and then isolate the protein responsible for the induction of sinusoids. We have also determined the DNA sequence of our own genome. Proteomics, the new field of biochemistry established as a partner with genomics, is dedicated to describing all the proteins that an organism’s genes encode, the key to achieving this goal. For example, we have learned that our own genome encodes around twenty-seven thousand different proteins. We need to describe each one of those proteins before we can begin to make sense of how our genes work to produce an organism as complex as a human being. Since all other life on Earth has a similar genome, we aspire to describe all their genes and all their proteins, too.
Inserting our gene of choice into the pig embryo has been worked out for many other systems and does not present any technical barriers that need to be overcome before proceeding. Completing the rest of the story would involve many clinical trials and lots of hard work on the part of clinicians. Fortunately, we scientists are up for the task. All we need to do is obtain funding for the project; no easy feat in today’s world of tight National Institutes of Health budgets and targeted research programs, and therein is the rub. High-risk proposals such as the one I have suggested fall well outside the guidelines of traditional funding streams, but the rewards would be great if they were to succeed. Here’s a good example of where our reach should exceed our grasp. If we learn to listen closely, the parasites will share their innermost secretes with us.