Did natural selection build in adaptive therapy for cancer?

Did natural selection build in adaptive therapy for cancer?

A new article proposes that adaptive therapy for cancer has been there all along as one of the body’s ways of preventing cancer. 

Thomas, F., Donnadieu, E., Charriere, G. M., Jacqueline, C., Tasiemski, A., Pujol, P., … Ujvari, B. (2018). Is adaptive therapy natural? PLOS Biology, 16(10), e2007066. https://doi.org/10.1371/journal.pbio.2007066

Abstract: Research suggests that progression-free survival can be prolonged by integrating evolutionary principles into clinical cancer treatment protocols. The goal is to prevent or slow the proliferation of resistant malignant cell populations. The logic behind this therapy relies on ecological and evolutionary processes. These same processes would be available to natural selection in decreasing the probability of an organism’s death due to cancer. We propose that organisms’ anticancer adaptions include not only ones for preventing cancer but also ones for directing and retarding the evolution of life-threatening cancer cells. We term this last strategy natural adaptive therapy (NAT). The body’s NAT might include a lower than otherwise possible immune response. A restrained immune response might forego maximum short-term kill rates. Restraint would forestall immune-resistant cancer cells and produce long-term durable control of the cancer population. Here, we define, develop, and explore the possibility of NAT. The discovery of NAT mechanisms could identify new strategies in tumor prevention and treatments. Furthermore, we discuss the potential risks of immunotherapies that force the immune system to ramp up the short-term kill rates of malignant cancer cells in a manner that undermines the body’s NAT and accelerates the evolution of immune resistance.

Cancer transmission via the placenta

Cancer transmission via the placenta

Greaves M, Hughes W. Cancer cell transmission via the placenta. Evolution, Medicine, and Public Health. 2018 Jan 1;2018(1):106–15. (open access

Abstract: Cancer cells have a parasitic propensity in the primary host but their capacity to transit between individuals is severely restrained by two factors: a lack of a route for viable cell transfer and immune recognition in allogeneic, secondary recipients. Several examples of transmissible animal cancers are now recognised. In humans, the only natural route for transmission is via the haemochorial placenta which is permissive for cell traffic. There are three special examples of this occurring in utero: maternal to foetus, intraplacental twin to twin leukaemias and choriocarcinoma-extra-embryonic cells to mother. We discuss the rare circumstances under which such transmission occurs.

Influenza and One Health 100 years after the Epidemic

Influenza and One Health 100 years after the Epidemic

Bailey, E. S., Choi, J. Y., Fieldhouse, J. K., Borkenhagen, L. K., Zemke, J., Zhang, D., & Gray, G. C. (2018). The continual threat of influenza virus infections at the human–animal interface. Evolution, Medicine, and Public Health, 2018(1), 192–198. https://doi.org/10.1093/emph/eoy013

Abstract: This year, in 2018, we mark 100 years since the 1918 influenza pandemic. In the last 100 years, we have expanded our knowledge of public health and increased our ability to detect and prevent influenza; however, we still face challenges resulting from these continually evolving viruses. Today, it is clear that influenza viruses have multiple animal reservoirs (domestic and wild), making infection prevention in humans especially difficult to achieve. With this report, we summarize new knowledge regarding influenza A, B, C and D viruses and their control. We also introduce how a multi-disciplinary One Health approach is necessary to mitigate these threats. 1. Bailey ES, Choi JY, Fieldhouse JK, Borkenhagen LK,

Does competition reduce drug resistance?

Does competition reduce drug resistance?

Huijben, S., Chan, B. H., Nelson, W. A., & Read, A. F. (2018). The impact of within-host ecology on the fitness of a drug-resistant parasite. Evolution, Medicine, and Public Health2018(1), 127-137.

Background and objectives: The rate of evolution of drug resistance depends on the fitness of resistant pathogens. The fitness of resistant pathogens is reduced by competition with sensitive pathogens in untreated hosts and so enhanced by competitive release in drug-treated hosts. We set out to estimate the magnitude of those effects on a variety of fitness measures, hypothesizing that competitive suppression and competitive release would have larger impacts when resistance was rarer to begin with. Methodology: We infected mice with varying densities of drug-resistant Plasmodium chabaudi malaria parasites in a fixed density of drug-sensitive parasites and followed infection dynamics using strain-specific quantitative PCR. Results: Competition with susceptible parasites reduced the absolute fitness of resistant parasites by 50–100%. Drug treatment increased the absolute fitness from 2- to >10 000-fold. The ecological context and choice of fitness measure was responsible for the wide variation in those estimates. Initial population growth rates poorly predicted parasite abundance and transmission probabilities. Conclusions and implications: (i) The sensitivity of estimates of pathogen fitness to ecological context and choice of fitness measure make it difficult to derive field-relevant estimates of the fitness costs and benefits of resistance from experimental settings. (ii) Competitive suppression can be a key force preventing resistance from emerging when it is rare, as it is when it first arises. (iii) Drug treatment profoundly affects the fitness of resistance. Resistance evolution could be slowed by developing drug use policies that consider in-host competition.

Ticks, meat allergies, and modern dysbiosis

Ticks, meat allergies, and modern dysbiosis

A most intriguing  article by Moises Velasquez-Manoff showed up in this week’s NY Times magazine. It starts with the new data showing that meat allergy can be precipitated by a tick bite. Alpha-gal (Galactose-alpha-1,3,-galactose) is present in other mammals but not humans. So, if a tick transmits the antigen, we can become allergic to meat.

But the article goes much further using smooth prose to integrate findings from many studies, also asking why mean allergies are becoming more common now. Is it more tick bites?  Or changed microbiomes?   Wonderful science writing about evolutionary medicine.

What the Mystery of the Tick-Borne Meat Allergy Could Reveal 
By Moises Velasquez-Manoff   NY Times July 23, 2018
One spring evening in 2016, Lee Niegelsky’s underarm began to itch. An investment manager, he was doing housework around his condo, and he thought he’d been bitten by a chigger. But within 15 minutes, hives had erupted all over his body. He responded with what he calls a “typical man reaction” — if the hives didn’t clear up by the next day, he would have them checked. Fifteen minutes later, the itch had become unbearable. He needed help right away. …Read the article at NYTimes.com

Amyloid Beta is a Feature not a Flaw

Amyloid Beta is a Feature not a Flaw

Amyloid beta is turning out to be an effective antimicrobial not a rouge dangerous byproduct. The slowness to recognize its function illustrates  the danger of pursing only proximate explanations without thinking deeply about why selection shaped mechanisms to make such a molecule. Two new papers this month clinch the case. ALZforum offers a lovely succinct summary of these advances.

A paper by Readhead et al. published June 21 in Neuron shows herpesviruses 6 and 7 are more common in brains with Alzheimer’s than those of controls. A paper due out July 11 from the Tanzi and Moir group at Mass General clinches the case. “herpesvirus glycoprotein B binding induces Aβ fibrillization, mediating protective activities against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6 (HHV6).” Details below.

Readhead B, Haure-Mirande JV, Funk CC, Richards MA, Shannon P, Haroutunian V, Sano M, Liang WS, Beckmann ND, Price ND, Reiman EM, Schadt EE, Ehrlich ME, Gandy S, Dudley JT. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron 99, 1–19 

Eimer WA, Kumar DK, Shanmugam NK, Washicosky KJ, Rodriguez AS, György B, Breakefield XO, Tanzi RO, Moir RD.Alzheimer’s disease-associated β-amyloid is rapidly seeded by herpesviridae to protect against brain infection. Neuron. 2018 Jul 11.