Adjuvants May Hold Key To Unlocking Cancer Immunotherapy Revolution
The FDA approval of sipuleucel-T (Provenge), a patient-specific immunotherapy for androgen independent prostate cancer developed by Dendreon Corporation (DNDN), and ipilimumab (Yervoy), the first immune check point molecule for melanoma by Bristol-Myers Squibb (BMY), has renewed interest in the concept of immunotherapy as an approach to cancer treatment. Often overlooked, however, adjuvants can be an essential part of an effective vaccine and could help advance the field even further.
Adjuvants are substances that can:
Accelerate the generation of robust, longer lasting immune responses
Generate antibodies with increased avidity and neutralization capacity
Enhance immune responses in individuals with weakened immune systems
Reduce the amount of antigen and number of doses needed, reducing the cost of vaccination programs
Activate the cellular arm of the adaptive response, specifically T helper type 1 and cytotoxic T cell responses
For next generation cancer vaccines that require T cell immunity or a broader range of antibody response, adjuvants are playing an essential and central role. For example, GlaxoSmithKline’s (GSK) melanoma antigen epitope-3 (MAGE-A3) antigen-specific cancer immunotherapeutic (ASCI) uses the company’s AS15 adjuvant system [1], which incorporates three different adjuvants (QS-21, MPL, and CpG) and is currently in pivotal Phase III trials for both non-small cell lung cancer (NSCLC) and melanoma with data expected in 2012.
History
During the last 80 years many adjuvants have been used in experimental settings, but due to various shortcomings of most of them only three have made it into regular clinical usage [2] – largely for infectious diseases. Of the three adjuvants, only two have been used in vaccines licensed by the U.S. Food and Drug Administration.
Alum (1930s)
For infectious disease vaccines, the most commonly used adjuvants are aluminum salt based (aluminum phosphate and aluminum hydroxide, alum), which are safe and effective for antibody induction. Alum is a component of many licensed human vaccines, including diphtheria-pertussis-tetanus (DPT), diphtheria-tetanus (DT), DT combined with Hepatitis B virus (HBV), Haemophilus influenza B or inactivated polio virus (IPV), hepatitis A (HAV), Streptococcus pneumonia, meningococcal, and human papilloma virus (HPV).
MF59 (1997)
MF59 is a potent vaccine adjuvant that has been licensed for more than 13 years for use in an influenza vaccine focused on elderly subjects (Fluad) by Novartis (NVS) [3]. It consists of an oil-in-water nano-emulsion composed of shark oil (squalene). It is licensed in Europe for use in influenza vaccines, but not in the U.S.
MPL (2009)
MPL (monophosphoryl lipid A) is a derivative of bacterial endotoxin and a potent immunostimulant. MPL was the second FDA licensed adjuvant molecule and is used in Cervarix by GlaxoSmithKline (GSK), which is a prophylactic vaccine against HPV types 16 and 18. GlaxoSmithKline obtained MPL through the $300 million acquisition of Corixa Corporation in 2005. MPL is also the first and only toll-like receptor (TLR) ligand approved in a human vaccine. TLRs are a class of proteins that play a key role in the innate immune system [4].
Few adjuvants approved
Adjuvants do not receive FDA approval as stand-alone products, but rather as part of a registered vaccine adjuvant–antigen combination [5]. The fact that safety regulations are often much more stringent with vaccines, as they are prophylactic and the main targets are often pediatric patients, partly explains why there are so few adjuvants approved to date [6].
Several recent developments have favorably altered the landscape for adjuvant development. First, GSK’s Cervarix vaccine received approval in 2009 and contained the first adjuvant (MPL) licensed by the FDA since the approval of Alum back in the 1930s. The second development has been FDA approval of sipuleucel-T (Provenge) by Dendreon and ipilimumab (Yervoy) by Bristol-Myers Squibb, which has renewed interest in the concept of immunotherapy as an approach to cancer treatment. In the cancer setting, adjuvants are being tested as part of a therapeutic vaccine as opposed to being use as a prophylactic vaccine, which may result in a shorter duration of exposure and reduced safety concerns. Third, if an influenza pandemic were to occur, such as the 2009-10 H1N1 pandemic, the potential vaccine supply would fall several billion doses short of the amount needed to provide protection to the global population [7]. The antigen-sparing effect of adjuvants could allow for expansion of vaccine supply to meet the necessary global demands during a pandemic, as evidenced by supporting grants from the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services.
Investigational adjuvants
Several companies are developing promising new candidates that may finally adjunct or displace aluminum substances as a popular adjuvant:
Agenus (AGEN)
Agenus Inc. (AGEN) is developing QS-21, a saponin extracted from the bark of the Quillaja saponaria tree, also known as the soap bark tree or Soapbark, an evergreen tree native to warm temperate central Chile. (Author's note: Agenus is a client of MD Becker Partners.) Quillaia raw material has been used for decades as an ingredient to create the foaming in beverages such as root beer, low-alcohol beers and foaming carbonated beverages. It has also been widely used as an adjuvant in veterinary vaccines.
QS-21 has extensive clinical experience with thousands of patients receiving vaccines containing QS-21 adjuvant. Agenus has licensed QS-21 to various Big Pharma partners and today there are 15 vaccine candidates using QS-21 in clinical development for infectious diseases, oncology, and central nervous system disorders, including the following Phase III programs by GlaxoSmithKline that could address large markets:
MAGE-A3 ASCI vaccine candidate, which is being studied in the largest-ever trial in the adjuvant treatment of NSCLC and also in Phase III trials for melanoma, with data expected in 2012.
Mosquirix (RTS,S), the world’s most advanced malaria vaccine candidate, with Phase III data expected by the end of 2011
Agenus is entitled to receive milestone payments and royalties from corporate partners that have licensed QS-21.
Antigen Express, Inc., a wholly-owned subsidiary of Generex Biotechnology Corporation (GNBT)
Antigen Express is advancing its proprietary Ii-Key hybrid technology. (Author's note: Antigen Express is a client of MD Becker Partners.) Ii-Key modification entails attaching a four-amino acid peptide (LRMK) to virtually any antigen and results in increased stimulation of CD4+ helper T cells and a more robust specific response to the antigen. Using this technology platform, Antigen Express is building a deep pipeline of therapeutics aimed at a variety of major diseases, including cancer, infectious diseases and autoimmune-based syndromes.
The company’s lead product candidate using Ii-Key modification is AE37, a peptide vaccine derived from a fragment of the HER-2/neu protein, which is expressed in a variety of tumors including 75-80% of breast cancers as well as a high percentage of prostate, ovarian and other cancers [8].
A controlled, randomized, and single-blinded Phase II clinical study of AE37 in HER-2 expressing breast cancer patients is currently underway to establish clinical efficacy. The study endpoint is a reduction in cancer relapse after two years compared to the current standard of care treatment. There are currently over 200 patients enrolled in the study with either node positive or high-risk node-negative breast cancer.
Celldex Therapeutics (CLDX) and 3M Company (MMM)
3M Drug Delivery Systems has a portfolio of patent protected TLR agonists that have shown promise as vaccine adjuvants. The lead candidate, resiquimod (TLR7/8 agonist) has shown promising results in a number of animal models and has an extensive toxicology and clinical data package to support further development as a vaccine adjuvant.
Celldex Therapeutics entered into a non-exclusive clinical research collaboration with 3M Drug Delivery Systems to access resiquimod for clinical study with the company’s Antigen Presenting Cell (APC) Targeting Technology in exchange for an undisclosed licensing fee, milestones and royalties. Celldex is developing CDX-1401, a fusion protein consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen, which is currently in a Phase I/II trial in combination with immune stimulating agents (resiquimod and/or poly-ICLC) for advanced cancers of the bladder, breast, ovary, non-small cell lung cancer, myeloma, sarcoma or melanoma.
Colby Pharmaceutical Company (private) and Juvaris BioTherapeutics
In September 2011, Juvaris BioTherapeutics, Inc. entered into an exclusive license agreement with Colby Pharmaceutical Company for the worldwide development and commercialization of Juvaris’ Cationic Lipid-DNA Complex (CLDC) technology and related JVRS-100 product candidate. Gene array studies with JVRS-100 show up-regulation of multiple immune response pathways compared to competing technologies. When combined with a vaccine antigen, JVRS-100 stimulates the adaptive immune response including specific antibodies and T-cell responses.
Idera Pharmaceuticals (IDRA)
Idera is developing numerous compounds that act as agonists for TLRs 3, 7, 8, or 9, which the company believes have the potential to be used as adjuvants in vaccines. In preclinical animal models, Idera’s TLR agonists have shown adjuvant activity when combined with various types of antigens.
In December 2007, Idera entered into an exclusive, worldwide licensing and collaboration agreement with Merck KGaA for the research, development and commercialization of Idera’s TLR9 agonists, including IMO-2055, for the treatment of cancer, excluding vaccines. Merck KGaA refers to IMO-2055 as EMD 1201081.
Merck KGaA expects to complete an ongoing Phase 2 clinical trial of IMO-2055 in combination with cetuximab (Erbitux) in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). However, based on increased incidence of neutropenia and electrolyte imbalances reported in its Phase 1 trial of IMO-2055 in combination with cisplatin/5-FU and cetuximab in patients with first-line SCCHN and subsequent re-evaluation of its clinical development program, in July 2011 Merck KGaA informed Idera that it will not conduct further clinical development of IMO-2055.
Immune Design Corporation (private)
Founded by the co-founder of Corixa Corporation, Immune Design Corporation is developing its proprietary adjuvant known as glucopyranosyl lipid A (GLA). GLA is a novel, clinical-stage, human TLR-4 agonist, representing the next generation of MPL. According to the company, GLA is unique because it is a pure synthetic small molecule, straightforward to manufacture with excellent stability, rationally designed to optimally activate human TLR-4 receptors, induces Th1 CD4 helper cells and elicits broad humoral immunity and active in multiple formulations and compatible with most antigens. GLA was also shown to be safe and well-tolerated in humans subjects in a Phase I clinical study in combination with the influenza virus vaccine Fluzone by Sanofi Pasteur, the vaccines division of sanofi-aventis Group (SNY). Immune Design Corporation is developing its own proprietary pipeline of vaccine candidates formulated with the GLA adjuvant for evaluation in further human clinical trials.
Vical Inc. (VICL)
Vical is developing Vaxfectin, a novel proprietary cationic lipid-based formulation that has been shown to effectively enhance plasmid DNA-based (as well as protein- and peptide-based) vaccines. It is a commixture of a cationic lipid (GAP-DMORIE) and a neutral phospholipid (DPyPE) which, when combined in an aqueous vehicle, self-assemble to form liposomes. In mechanism of action studies, Vaxfectin has been shown to increase a number of cytokines and chemokines, while toll-like receptor signaling was contributory.
Vical is developing several products that utilize Vaxfectin as an adjuvant. These include CyMVectin, the company’s prophylactic vaccine against cytomegalovirus (CMV) infection, and its pandemic influenza vaccines.
Conclusion
Beyond their established role in infectious diseases, adjuvants will also likely become important in cancer immunotherapy where they will be critical for targeting weakly immunogenic tumor antigens in order to overcome various tolerance mechanisms and facilitate induction of cytotoxic T lymphocytes. Several promising new adjuvants are currently being developed that offer superior properties and a set of desired characteristics, with clinical data expected in the near future.
The topic of adjuvants in cancer immunotherapy will covered in an upcoming panel session at the second annual Cancer Immunotherapy: A Long-Awaited Reality conference being held in New York City on October 6, 2011.
References
[1] Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Garçon N, Van Mechelen M. Expert Rev Vaccines. 2011 Apr;10(4):471-86. Review.
[2] The ABC of clinical and experimental adjuvants–a brief overview. Brunner R, Jensen-Jarolim E, Pali-Schöll I. Immunol Lett. 2010 Jan 18;128(1):29-35. Epub 2009 Nov 4.
[3] MF59 adjuvant: the best insurance against influenza strain diversity. O’Hagan DT, Rappuoli R, De Gregorio E, Tsai T, Del Giudice G. Expert Rev Vaccines. 2011 Apr;10(4):447-62.
[4] Impaired TLR3/IFN-beta signaling in monocyte-derived dendritic cells from patients with acute-on-chronic hepatitis B liver failure: relevance to the severity of liver damage. Li N, Li Q, Qian Z, Zhang Y, Chen M, Shi G. Biochem Biophys Res Commun. 2009 Dec 18;390(3):630-5. Epub 2009 Oct 13.
[5] Adjuvants for malaria vaccines. Coler RN, Carter D, Friede M, Reed SG. Parasite Immunol. 2009 Sep;31(9):520-8. Review.
[6] Delivery Technologies for Biopharmaceuticals: Peptides, Proteins, Nucleic Acids and Vaccines edited by Lene Jorgensen and Hanne Mørck Nielsen
[7] Global pandemic influenza action plan to increase vaccine supply by the World Health Organization at http://www.who.int/vaccines-documents/DocsPDF06/863.pdf
[8] AE37: a novel T-cell-eliciting vaccine for breast cancer. Sears AK, Perez SA, Clifton GT, Benavides LC, Gates JD, Clive KS, Holmes JP, Shumway NM, Van Echo DC, Carmichael MG, Ponniah S, Baxevanis CN, Mittendorf EA, Papamichail M, Peoples GE.
Tuesday, September 20, 2011
Saturday, August 20, 2011
U.S. Scrambling to Ease Shortage of Vital Medicine
By GARDINER HARRIS
WASHINGTON — Federal officials and lawmakers, along with the drug industry and doctors’ groups, are rushing to find remedies for critical shortages of drugs to treat a number of life-threatening illnesses, including bacterial infection and several forms of cancer.
The proposed solutions, which include a national stockpile of cancer medicines and a nonprofit company that will import drugs and eventually make them, are still in the early or planning stages. But the sense of alarm is widespread.
“These shortages are just killing us,” said Dr. Michael Link, president of the American Society of Clinical Oncology, the nation’s largest alliance of cancer doctors. “These drugs save lives, and it’s unconscionable that medicines that cost a couple of bucks a vial are unavailable.”
So far this year, at least 180 drugs that are crucial for treating childhood leukemia, breast and colon cancer, infections and other diseases have been declared in short supply — a record number.
Prices for some have risen as much as twentyfold, and clinical trials for some experimental cures have been delayed because the studies must also offer older medicines that cannot be reliably provided.
On Wednesday, Dianne Nomikos, 65, went to M. D. Anderson Cancer Center in Houston for a 9 a.m. appointment to receive Doxil, a vital medicine for her ovarian cancer. She was told to go home and wait until new supplies arrived.
“My life is in jeopardy,” she said through tears in a telephone interview. “Without the drug, who knows what’s going to happen to me?”
The Obama administration is considering creating a government stockpile of crucial cancer medicines. The Centers for Disease Control and Prevention already stockpile antibiotics, antidotes and other drugs needed in the event of a terrorist attack or earthquake.
Under one plan, the government would store the dry ingredients for cancer drugs and, in the face of a shortage, distribute them to hospitals, where pharmacists could mix them into injectable compounds.
Dr. Richard Schilsky, a professor of medicine at the University of Chicago, said the number of cancers diagnosed in a year was easy to predict. “So we ought to be able to make a pretty good estimate of the grams required to treat every patient in the country in any given year,” he said.
Legislation proposed in both the House and the Senate would give the Food and Drug Administration the power to demand that drug makers give early warnings of possible supply disruptions. Senator Amy Klobuchar, Democrat of Minnesota, said the idea behind the bipartisan bill came after she found that the agency had prevented 38 shortages last year after getting early alerts of problems at drug makers.
“I can’t say the drug companies are excited” about the proposed legislation, she said in an interview. “But we need to give the F.D.A. more time.”
A group of leading oncologists has started a not-for-profit drug company that it hopes will soon be able to import supplies of some of the missing medicines. The company will eventually manufacture the drugs itself, according to Dr. George Tidmarsh, a pediatric oncologist and biotechnology entrepreneur who will lead it.
“We have a meeting with the F.D.A. next week,” Dr. Tidmarsh said. “This unfolding tragedy must stop, and right now.”
More than half the recent shortages have resulted because government or company inspectors found problems like microbial contamination that can be lethal on injection. Others have occurred because of capacity problems at drug plants or lack of interest because of low profits, according to the F.D.A.
Doxil, the cancer drug Ms. Nomikos needs, is made by Johnson & Johnson. Monica Neufang, a company spokeswoman, said, “Our third-party manufacturer has had some manufacturing issues related to capacity.”
Heather Bresch, president of the generic drug giant Mylan, says the shortages grow out of a sweeping consolidation of the generic drug industry into a few behemoths that compete only on price and have foreign plants that are rarely inspected.
“The race to the bottom has led to an increase of products coming from plants in China and India that may have uncertain supply and may have never been inspected,” Ms. Bresch said. “If the F.D.A. was required to inspect foreign drug plants at the same rate it does domestic ones, we might not have so many of these shortages.”
Ms. Bresch has helped to broker an agreement that would require the industry to pay $299 million a year for increased inspections of foreign drug plants, a deal that must be approved by Congress and one she says will prevent some shortages.
Top government officials have held a blizzard of meetings in recent weeks to tackle the shortage issue, and more are expected over the next month — including a public advisory meeting at the F.D.A. and hearings in Congress.
“Drug shortages represent a pressing public health issue, and we are actively working to understand the causes, the full scope of the problem in the U.S. and internationally, and possible solutions,” said Dr. Howard K. Koh, an assistant secretary for health.
A crucial problem is disconnection between the free market and required government regulation. Prices for many older medicines are low until the drugs are in short supply; then prices soar. But these higher prices do little to encourage more supply, because it can be difficult and expensive to overcome the technical and regulatory hurdles. And if supplies return to normal, prices plunge.
Executives at Premier, a hospital buying cooperative, said that in April and May its members received hundreds of offers from obscure drug wholesalers to sell drugs in short supply at vastly inflated prices. Of the 636 offers that included a price, 45 percent were at least 10 times the normal rate and 27 percent were at least 20 times normal.
Such sales offers are legal as long as suppliers prove that they bought the drugs appropriately. Some wholesalers buy certain drugs in large quantities because they are betting there will be a shortage. The excessive buying can help make their predictions come true. “We never like to see a situation where people can profit off of a national crisis and engage in price gouging,” Mike Alkire, Premier’s chief operating officer, said in an interview.
Joyce Burke, 47, of Mooresville, N.C., has breast cancer and is worried that she might not be able to get Taxol, which is in short supply. A drug that might have been substituted for Taxol has a side effect that leads some patients to lose their fingernails.
“I was not looking forward to losing my fingernails,” she said.
On Thursday, she received her first dose of Taxol, and her doctor said he had secured enough of the drug to give her a second dose in a little more than a week. She will need four doses to complete the treatment.
“And I asked, ‘What happens if you can’t find the rest?’ ” Ms. Burke said. “It’s not nearly as effective if you switch drugs midway through.”
WASHINGTON — Federal officials and lawmakers, along with the drug industry and doctors’ groups, are rushing to find remedies for critical shortages of drugs to treat a number of life-threatening illnesses, including bacterial infection and several forms of cancer.
The proposed solutions, which include a national stockpile of cancer medicines and a nonprofit company that will import drugs and eventually make them, are still in the early or planning stages. But the sense of alarm is widespread.
“These shortages are just killing us,” said Dr. Michael Link, president of the American Society of Clinical Oncology, the nation’s largest alliance of cancer doctors. “These drugs save lives, and it’s unconscionable that medicines that cost a couple of bucks a vial are unavailable.”
So far this year, at least 180 drugs that are crucial for treating childhood leukemia, breast and colon cancer, infections and other diseases have been declared in short supply — a record number.
Prices for some have risen as much as twentyfold, and clinical trials for some experimental cures have been delayed because the studies must also offer older medicines that cannot be reliably provided.
On Wednesday, Dianne Nomikos, 65, went to M. D. Anderson Cancer Center in Houston for a 9 a.m. appointment to receive Doxil, a vital medicine for her ovarian cancer. She was told to go home and wait until new supplies arrived.
“My life is in jeopardy,” she said through tears in a telephone interview. “Without the drug, who knows what’s going to happen to me?”
The Obama administration is considering creating a government stockpile of crucial cancer medicines. The Centers for Disease Control and Prevention already stockpile antibiotics, antidotes and other drugs needed in the event of a terrorist attack or earthquake.
Under one plan, the government would store the dry ingredients for cancer drugs and, in the face of a shortage, distribute them to hospitals, where pharmacists could mix them into injectable compounds.
Dr. Richard Schilsky, a professor of medicine at the University of Chicago, said the number of cancers diagnosed in a year was easy to predict. “So we ought to be able to make a pretty good estimate of the grams required to treat every patient in the country in any given year,” he said.
Legislation proposed in both the House and the Senate would give the Food and Drug Administration the power to demand that drug makers give early warnings of possible supply disruptions. Senator Amy Klobuchar, Democrat of Minnesota, said the idea behind the bipartisan bill came after she found that the agency had prevented 38 shortages last year after getting early alerts of problems at drug makers.
“I can’t say the drug companies are excited” about the proposed legislation, she said in an interview. “But we need to give the F.D.A. more time.”
A group of leading oncologists has started a not-for-profit drug company that it hopes will soon be able to import supplies of some of the missing medicines. The company will eventually manufacture the drugs itself, according to Dr. George Tidmarsh, a pediatric oncologist and biotechnology entrepreneur who will lead it.
“We have a meeting with the F.D.A. next week,” Dr. Tidmarsh said. “This unfolding tragedy must stop, and right now.”
More than half the recent shortages have resulted because government or company inspectors found problems like microbial contamination that can be lethal on injection. Others have occurred because of capacity problems at drug plants or lack of interest because of low profits, according to the F.D.A.
Doxil, the cancer drug Ms. Nomikos needs, is made by Johnson & Johnson. Monica Neufang, a company spokeswoman, said, “Our third-party manufacturer has had some manufacturing issues related to capacity.”
Heather Bresch, president of the generic drug giant Mylan, says the shortages grow out of a sweeping consolidation of the generic drug industry into a few behemoths that compete only on price and have foreign plants that are rarely inspected.
“The race to the bottom has led to an increase of products coming from plants in China and India that may have uncertain supply and may have never been inspected,” Ms. Bresch said. “If the F.D.A. was required to inspect foreign drug plants at the same rate it does domestic ones, we might not have so many of these shortages.”
Ms. Bresch has helped to broker an agreement that would require the industry to pay $299 million a year for increased inspections of foreign drug plants, a deal that must be approved by Congress and one she says will prevent some shortages.
Top government officials have held a blizzard of meetings in recent weeks to tackle the shortage issue, and more are expected over the next month — including a public advisory meeting at the F.D.A. and hearings in Congress.
“Drug shortages represent a pressing public health issue, and we are actively working to understand the causes, the full scope of the problem in the U.S. and internationally, and possible solutions,” said Dr. Howard K. Koh, an assistant secretary for health.
A crucial problem is disconnection between the free market and required government regulation. Prices for many older medicines are low until the drugs are in short supply; then prices soar. But these higher prices do little to encourage more supply, because it can be difficult and expensive to overcome the technical and regulatory hurdles. And if supplies return to normal, prices plunge.
Executives at Premier, a hospital buying cooperative, said that in April and May its members received hundreds of offers from obscure drug wholesalers to sell drugs in short supply at vastly inflated prices. Of the 636 offers that included a price, 45 percent were at least 10 times the normal rate and 27 percent were at least 20 times normal.
Such sales offers are legal as long as suppliers prove that they bought the drugs appropriately. Some wholesalers buy certain drugs in large quantities because they are betting there will be a shortage. The excessive buying can help make their predictions come true. “We never like to see a situation where people can profit off of a national crisis and engage in price gouging,” Mike Alkire, Premier’s chief operating officer, said in an interview.
Joyce Burke, 47, of Mooresville, N.C., has breast cancer and is worried that she might not be able to get Taxol, which is in short supply. A drug that might have been substituted for Taxol has a side effect that leads some patients to lose their fingernails.
“I was not looking forward to losing my fingernails,” she said.
On Thursday, she received her first dose of Taxol, and her doctor said he had secured enough of the drug to give her a second dose in a little more than a week. She will need four doses to complete the treatment.
“And I asked, ‘What happens if you can’t find the rest?’ ” Ms. Burke said. “It’s not nearly as effective if you switch drugs midway through.”
Thursday, January 6, 2011
Is eating too many smoked and cured foods bad for me?
Dr Thomas Stuttaford
A 55-year-old reader from Chiswick has written to ask if eating cured foods, especially smoked cured foods, is dangerous. He fears that they may represent an appreciable medical hazard. He especially enjoys eating traditionally wood-smoked bacon, ham, chicken breast and kippers. He always prefers wood smoked products to unsmoked cured meats, but wonders if this is a wise decision.
Our reader shares a similar palate to my own. However, unlike him I am able to enjoy smoked goose breast or Yarmouth bloaters without worrying about the possibility that the cancer-forming (carcinogenic) chemicals found in cured meats or fish represent a significant danger to the ordinary diner.
For rather than being concerned about the curing process, which is well controlled by manufacturers, I am grateful that the salt and sodium nitrite used in the process deal a death blow to any Clostridium botulinum present. This is the bacterium that can cause botulism, a form of food poisoning that can have devastating, even occasionally fatal, results. The curing process also stops the meat going bad.
Most cured meats contain nitrosamines. These are formed when amines — breakdown constituents of proteins — are mixed with the sodium nitrite that, with salt (sodium chloride), is used to cure and preserve meat. The combination of small quantities of salt and sodium nitrite is such an effective mixture in preventing food poisoning and preserving the meat that no comparable alternative has been found.
Although there is evidence that nitrosamines are carcinogenic, it is doubtful if, in the small amounts the average person takes, it increases appreciably the risk of developing cancer after exposure to cured ham, bacon, other meats and fish. Choosing smoked meats and fish as an occasional hors d’oeuvre, or even having them as a main course from time to time, is unlikely to be significant. Research suggests that most people derive far more nitrates from vegetables, including such old faithfuls as spinach and cabbages, than from cured meats. It is estimated that only 1 per cent of someone’s nitrite concentration in the gut has been derived from cured meats and 90 per cent from vegetables. Nitrates are reduced to nitrites by organisms in the intestinal tract. Even so, it wouldn’t be considered a good idea to dine exclusively on cured and smoked foods.
Anxious lovers of smoked foods may also worry about the effect of benzopyrenes — potentially potent carcinogens — produced by smoking food. In smoked foods the levels of these may exceed 50 micrograms per kilogram. The relevant factor in considering possible problems caused either by the curing with salt and sodium nitrite or by the benzopyrenes from smoking is the amount of exposure to them. People who have a mixed diet can occasionally relish smoked foods without fearing that a few mouthfuls of smoked eel need to be followed by an immediate call to their local solicitor to update their will.
Those people who are obsessed with possible carcinogens in their food may also worry about the standard rasher or two of bacon in what hotels call the traditional English breakfast. They should perhaps choose to send back any burnt toast. Burnt toast, too, has a theoretical carcinogenic potential. Likewise, so has any unsaturated fat cooked at a high temperature. Research on cooking bacon has shown that the microwave is safer than the frying pan. The level of the nitrosopyrrolidines, a toxic substance produced by heating nitrosamines, is virtually undetectable when the bacon is cooked at a low temperature very slowly.
The crispier the bacon the higher the content of nitrosopyrrolidines. A medium well-done rasher cooked at 210F (99C) has ten times the quantity of nitrosopyrrolidines asmin slowly heated bacon. Cooked at 400F quickly, it has 17 times the amount and in crisped (virtually burnt) bacon there are 19 times as much nitrosopyrrolidines.
The good news is that the evidence that crispy bacon has ever harmed anyone is lacking. In fact there are more carcinogens in very hot fat. Another piece of reassuring news is that vitamin C in breakfast fruit juices may help to counteract nitrosamines.
A 55-year-old reader from Chiswick has written to ask if eating cured foods, especially smoked cured foods, is dangerous. He fears that they may represent an appreciable medical hazard. He especially enjoys eating traditionally wood-smoked bacon, ham, chicken breast and kippers. He always prefers wood smoked products to unsmoked cured meats, but wonders if this is a wise decision.
Our reader shares a similar palate to my own. However, unlike him I am able to enjoy smoked goose breast or Yarmouth bloaters without worrying about the possibility that the cancer-forming (carcinogenic) chemicals found in cured meats or fish represent a significant danger to the ordinary diner.
For rather than being concerned about the curing process, which is well controlled by manufacturers, I am grateful that the salt and sodium nitrite used in the process deal a death blow to any Clostridium botulinum present. This is the bacterium that can cause botulism, a form of food poisoning that can have devastating, even occasionally fatal, results. The curing process also stops the meat going bad.
Most cured meats contain nitrosamines. These are formed when amines — breakdown constituents of proteins — are mixed with the sodium nitrite that, with salt (sodium chloride), is used to cure and preserve meat. The combination of small quantities of salt and sodium nitrite is such an effective mixture in preventing food poisoning and preserving the meat that no comparable alternative has been found.
Although there is evidence that nitrosamines are carcinogenic, it is doubtful if, in the small amounts the average person takes, it increases appreciably the risk of developing cancer after exposure to cured ham, bacon, other meats and fish. Choosing smoked meats and fish as an occasional hors d’oeuvre, or even having them as a main course from time to time, is unlikely to be significant. Research suggests that most people derive far more nitrates from vegetables, including such old faithfuls as spinach and cabbages, than from cured meats. It is estimated that only 1 per cent of someone’s nitrite concentration in the gut has been derived from cured meats and 90 per cent from vegetables. Nitrates are reduced to nitrites by organisms in the intestinal tract. Even so, it wouldn’t be considered a good idea to dine exclusively on cured and smoked foods.
Anxious lovers of smoked foods may also worry about the effect of benzopyrenes — potentially potent carcinogens — produced by smoking food. In smoked foods the levels of these may exceed 50 micrograms per kilogram. The relevant factor in considering possible problems caused either by the curing with salt and sodium nitrite or by the benzopyrenes from smoking is the amount of exposure to them. People who have a mixed diet can occasionally relish smoked foods without fearing that a few mouthfuls of smoked eel need to be followed by an immediate call to their local solicitor to update their will.
Those people who are obsessed with possible carcinogens in their food may also worry about the standard rasher or two of bacon in what hotels call the traditional English breakfast. They should perhaps choose to send back any burnt toast. Burnt toast, too, has a theoretical carcinogenic potential. Likewise, so has any unsaturated fat cooked at a high temperature. Research on cooking bacon has shown that the microwave is safer than the frying pan. The level of the nitrosopyrrolidines, a toxic substance produced by heating nitrosamines, is virtually undetectable when the bacon is cooked at a low temperature very slowly.
The crispier the bacon the higher the content of nitrosopyrrolidines. A medium well-done rasher cooked at 210F (99C) has ten times the quantity of nitrosopyrrolidines asmin slowly heated bacon. Cooked at 400F quickly, it has 17 times the amount and in crisped (virtually burnt) bacon there are 19 times as much nitrosopyrrolidines.
The good news is that the evidence that crispy bacon has ever harmed anyone is lacking. In fact there are more carcinogens in very hot fat. Another piece of reassuring news is that vitamin C in breakfast fruit juices may help to counteract nitrosamines.
Friday, October 29, 2010
A Different Kind of Eyeglasses
By MICHAEL TOTTY
For many people past the age of 40, focusing on close objects—restaurant menus, for instance—just gets harder and harder.
Most people with this condition, called presbyopia, eventually give in and get reading glasses, bifocals or glasses with progressive lenses.
But what if there were another alternative that didn't require people to carry an extra set of glasses or have only part of their field of vision in focus at any one time?
Zoom Focus Eyewear LLC, of Van Nuys, Calif., has just such an option, and with it won this year's Silver Innovation Award. The solution: eyeglasses, called TruFocals, that the wearer can manually adjust to give clear, undistorted vision whether reading a book, working on a computer or looking into the distance.
The judges praised the potential large-scale benefit of TruFocals. Richard S. Lang, one of the judges and a physician at the Cleveland Clinic, called the technology a paradigm shift in the way it addresses a problem "that has been handled the same way for many years."
Mimicking the Eye
For more than 100 years, researchers have tried to come up with adjustable eyeglasses; a Baltimore inventor filed a patent on the idea in 1866. But a workable product that's easy to adjust, thin, lightweight and accurate proved elusive.
For the Wall Street Journal's 10th annual Tech Innovation Awards, Taiwan's Industrial Technology Research Institute received the Gold award for its technology to make paper-thin computer screens with a twist. The company beat out nearly 600 entries for its top ranking, along with Silver-award-winner Zoom Focus and Bronze-winner Counsyl of Silicon Valley.
Stephen Kurtin, a California inventor who previously devised one of the first word-processing programs, turned to the problem in the early 1990s. His solution, TruFocal eyeglasses, mimic the way that the lens of the human eye stretches and contracts to adjust focus.
Each TruFocal lens is actually a set of two lenses: an outer lens, and an inner lens made of a flat glass plate attached to a flexible membrane that contains a clear, silicone-based liquid. A manual slider on the bridge of the eyeglasses adjusts the focus by changing the shape of the membrane. The outer lens can be custom made to correct other vision problems besides presbyopia, including nearsightedness and astigmatism.
Once the TruFocal lenses are adjusted, the entire field of vision is in focus, unlike bifocals and progressive lenses, which keep only a limited area in sharp focus. So a user can adjust the glasses to focus only on the book he's reading, then look up and readjust them to focus solely on the TV across the room.
One Shape, Several Colors
There were some false starts along the way. Mr. Kurtin considered using liquid-crystal electronics to adjust the focus, but the batteries proved problematic. The first model weighed seven pounds. But after nearly 20 years of refinements, the first TruFocal glasses were introduced in 2009.
There's a downside for the fashion conscious: The glasses come in one shape—round—and have been compared to the spectacles worn by Harry Potter. (They are sold in several colors, though.) The circular lenses are necessary to the workings of the technology; with any other shape, the flexible membrane couldn't keep a spherical shape when compressed.
TruFocals aren't the only glasses with adjustable lenses. But other products are mainly designed for users in the developing world, where optometrists aren't widely available; they are meant to be adjusted once by the user to correct the focus at a given distance and then set that way. The Zoom Focus product is aimed at wearers who want to make constant adjustments in their vision.
Next month, TruFocals will be rebranded as Superfocus glasses. The company will also change its name, to Superfocus LLC.
For many people past the age of 40, focusing on close objects—restaurant menus, for instance—just gets harder and harder.
Most people with this condition, called presbyopia, eventually give in and get reading glasses, bifocals or glasses with progressive lenses.
But what if there were another alternative that didn't require people to carry an extra set of glasses or have only part of their field of vision in focus at any one time?
Zoom Focus Eyewear LLC, of Van Nuys, Calif., has just such an option, and with it won this year's Silver Innovation Award. The solution: eyeglasses, called TruFocals, that the wearer can manually adjust to give clear, undistorted vision whether reading a book, working on a computer or looking into the distance.
The judges praised the potential large-scale benefit of TruFocals. Richard S. Lang, one of the judges and a physician at the Cleveland Clinic, called the technology a paradigm shift in the way it addresses a problem "that has been handled the same way for many years."
Mimicking the Eye
For more than 100 years, researchers have tried to come up with adjustable eyeglasses; a Baltimore inventor filed a patent on the idea in 1866. But a workable product that's easy to adjust, thin, lightweight and accurate proved elusive.
For the Wall Street Journal's 10th annual Tech Innovation Awards, Taiwan's Industrial Technology Research Institute received the Gold award for its technology to make paper-thin computer screens with a twist. The company beat out nearly 600 entries for its top ranking, along with Silver-award-winner Zoom Focus and Bronze-winner Counsyl of Silicon Valley.
Stephen Kurtin, a California inventor who previously devised one of the first word-processing programs, turned to the problem in the early 1990s. His solution, TruFocal eyeglasses, mimic the way that the lens of the human eye stretches and contracts to adjust focus.
Each TruFocal lens is actually a set of two lenses: an outer lens, and an inner lens made of a flat glass plate attached to a flexible membrane that contains a clear, silicone-based liquid. A manual slider on the bridge of the eyeglasses adjusts the focus by changing the shape of the membrane. The outer lens can be custom made to correct other vision problems besides presbyopia, including nearsightedness and astigmatism.
Once the TruFocal lenses are adjusted, the entire field of vision is in focus, unlike bifocals and progressive lenses, which keep only a limited area in sharp focus. So a user can adjust the glasses to focus only on the book he's reading, then look up and readjust them to focus solely on the TV across the room.
One Shape, Several Colors
There were some false starts along the way. Mr. Kurtin considered using liquid-crystal electronics to adjust the focus, but the batteries proved problematic. The first model weighed seven pounds. But after nearly 20 years of refinements, the first TruFocal glasses were introduced in 2009.
There's a downside for the fashion conscious: The glasses come in one shape—round—and have been compared to the spectacles worn by Harry Potter. (They are sold in several colors, though.) The circular lenses are necessary to the workings of the technology; with any other shape, the flexible membrane couldn't keep a spherical shape when compressed.
TruFocals aren't the only glasses with adjustable lenses. But other products are mainly designed for users in the developing world, where optometrists aren't widely available; they are meant to be adjusted once by the user to correct the focus at a given distance and then set that way. The Zoom Focus product is aimed at wearers who want to make constant adjustments in their vision.
Next month, TruFocals will be rebranded as Superfocus glasses. The company will also change its name, to Superfocus LLC.
Thursday, October 28, 2010
Targeting tumors without the pain of radiation
Israeli scientists have developed an innovative new nano-particle treatment for cancerous tumors that could replace traditional radiation therapy.
Traditional radiation treatment has a range of damaging side effects, but Prof. Israel Gannot believes he can provide an alternative.
Scientists from Israel are developing a new way to destroy cancerous tumors that will have fewer side effects than traditional radiation therapy, and cause minimal damage to surrounding tissue.
The innovative method developed by a professor at Tel Aviv University uses heat to kill the tumor cells, while leaving the surrounding healthy tissue intact.
Today, radiation therapy is one of the most important weapons against cancerous tumors, but the therapy can have a significant impact on the health of a patient as it harms healthy tissue as well as malignant cells.
Patients often experience anything from nausea to hair loss, fatigue, skin irritation, and a lowered white blood cell count.
Prof. Israel Gannot, whose method is soon to be published in the journal Nanomedicine, uses a special mixture of nano-particles - already approved by the Food and Drug Administration (FDA) - and antibodies to locate individual tumors and bind directly to them.
A targeted rise in temperature
The specialized cocktail is administered safely and simply, through topical local injection or injection into the blood stream.
"Once the nano-particles bind to the tumor, we excite them with an external magnetic field, and they begin to heat very specifically and locally," Gannot explains. The magnetic field is manipulated to create a targeted rise in temperature, and it is this directed heat elevation that kills the tumors, he says.
Once the treatment is completed, the nano-particles are washed out of the body naturally without leaving a trace, minimizing side effects.
So far, the treatment has been proven effective against epithelial cancers, which can develop in almost any area of the body, such as the breast or lung. By using a special feedback process, also developed in his laboratory, the process can be optimized for individual treatment.
Gannot claims the method is effective against almost any type of tumor, as long as its specific markers and its antibodies can be identified.
Recuperation at home
Aside from being minimally invasive, Gannot says that the treatment is also fast and efficient. The entire treatment lasts only six hours, and can be administered during an out-patient procedure, enabling patients to recuperate in the comfort of their own homes.
It's early days yet, however. Gannot is currently applying his technique to cell lines and to ex vivo tissues and tissue-like substitutes in his lab, and plans to start in vivo experiments by next year.
If long-term clinical trials are successful, however, Gannot believes the technique could become a mainstay of patient care.
Traditional radiation treatment has a range of damaging side effects, but Prof. Israel Gannot believes he can provide an alternative.
Scientists from Israel are developing a new way to destroy cancerous tumors that will have fewer side effects than traditional radiation therapy, and cause minimal damage to surrounding tissue.
The innovative method developed by a professor at Tel Aviv University uses heat to kill the tumor cells, while leaving the surrounding healthy tissue intact.
Today, radiation therapy is one of the most important weapons against cancerous tumors, but the therapy can have a significant impact on the health of a patient as it harms healthy tissue as well as malignant cells.
Patients often experience anything from nausea to hair loss, fatigue, skin irritation, and a lowered white blood cell count.
Prof. Israel Gannot, whose method is soon to be published in the journal Nanomedicine, uses a special mixture of nano-particles - already approved by the Food and Drug Administration (FDA) - and antibodies to locate individual tumors and bind directly to them.
A targeted rise in temperature
The specialized cocktail is administered safely and simply, through topical local injection or injection into the blood stream.
"Once the nano-particles bind to the tumor, we excite them with an external magnetic field, and they begin to heat very specifically and locally," Gannot explains. The magnetic field is manipulated to create a targeted rise in temperature, and it is this directed heat elevation that kills the tumors, he says.
Once the treatment is completed, the nano-particles are washed out of the body naturally without leaving a trace, minimizing side effects.
So far, the treatment has been proven effective against epithelial cancers, which can develop in almost any area of the body, such as the breast or lung. By using a special feedback process, also developed in his laboratory, the process can be optimized for individual treatment.
Gannot claims the method is effective against almost any type of tumor, as long as its specific markers and its antibodies can be identified.
Recuperation at home
Aside from being minimally invasive, Gannot says that the treatment is also fast and efficient. The entire treatment lasts only six hours, and can be administered during an out-patient procedure, enabling patients to recuperate in the comfort of their own homes.
It's early days yet, however. Gannot is currently applying his technique to cell lines and to ex vivo tissues and tissue-like substitutes in his lab, and plans to start in vivo experiments by next year.
If long-term clinical trials are successful, however, Gannot believes the technique could become a mainstay of patient care.
Wednesday, October 20, 2010
In Israel, Growing Tobacco to Save Lives
By John Bernard
In a greenhouse in northern Israel, a company is growing tobacco plants yielding a surprising product that is vastly different from cigarettes. These plants produce genetically-engineered human collagen, a protein vital for tissue repair that is used by surgeons to fill bone voids in cancer patients, fix heart valves and heal severe wounds.
The genetic engineering technology that allows the tobacco plants to generate the collagen was developed by CollPlant based in Rehovot in central Israel. This novel use of the tobacco plant answers a major unmet medical need.
A scientific achievement with commercial potential
“Collagen is used in about a thousand important medical products, but until now manufacturers have had to derive it from pigs, cows or human corpses,” says CollPlant CEO Yehiel Tal, noting that the US Food and Drug Administration (FDA) and other international health regulatory agencies have expressed serious safety concerns with respect to the use of both animal and human corpse tissues.
CollPlant’s plant-derived collagen poses no safety risks and can be considered a green technology, eliminating the industrial waste and ecological damage associated with the raising of livestock. In addition, the company is providing tobacco farmers with a healthier and more lucrative use for their crops.
“The leaves of a single tobacco plant can yield about 100 grams of tobacco (for cigarettes) or about a gram of genetically-engineered human collagen,” says Prof. Oded Shoseyov, CollPlant’s co-founder and the inventor of the technology. “And from a single gram of collagen it is possible to produce, for example, about three injections of highly-valuable wound healing gel for patients suffering from diabetic ulcers.”
In developing CollPlant’s innovative technology, Shoseyov had to overcome a formidable scientific challenge. “Most proteins in the body are the result of a single gene but there are five different genes responsible for the production of collagen.”
Shoseyov’s success in transferring all five genes into a transgenic plant that could produce collagen was acknowledged earlier this year when he was awarded the prestigious Hebrew University Kaye Innovation Award for “scientific excellence with commercial potential.”
Good news from the FDA
CollPlant is well on the way to leveraging the commercial potential of Shoseyov’s invention. The company has begun to market collagen as a raw material to Japanese manufacturers and in August received good news from the FDA about its first product.
“The FDA informed us that they have agreed to classify our Vergenix wound dressing as a medical device, rather than as a drug or biologic product,” says Tal. “This is a breakthrough because the medical device regulatory review process is much simpler and quicker than that used for products defined as drugs or biologics.”
Vergenix is just the first of several regenerative tissue products in the CollPlant pipeline that target the multi-billion dollar wound management market. These products include gel formulations for deep-tunneled wounds associated with diabetic ulcers, as well as wound dressings for acute and chronic wounds.
Other CollPlant products will attempt to meet the growing demand for collagen-based orthopedic products. In the US alone, each year there are about 800,000 ligament and tendon repair procedures, 400,000 shoulder operations and more than 500,000 bone graft procedures, all of which require collagen.
CollPlant has received strong support from leading investors since its inception. Investment funds headed by two prominent healthcare industrialists, former Teva Pharmaceuticals CEO Eli Hurvitz and Perrigo founder Mory Arkin, were among the founding investors. Earlier this year the company began to trade publicly on the Tel Aviv Stock Exchange.
In a greenhouse in northern Israel, a company is growing tobacco plants yielding a surprising product that is vastly different from cigarettes. These plants produce genetically-engineered human collagen, a protein vital for tissue repair that is used by surgeons to fill bone voids in cancer patients, fix heart valves and heal severe wounds.
The genetic engineering technology that allows the tobacco plants to generate the collagen was developed by CollPlant based in Rehovot in central Israel. This novel use of the tobacco plant answers a major unmet medical need.
A scientific achievement with commercial potential
“Collagen is used in about a thousand important medical products, but until now manufacturers have had to derive it from pigs, cows or human corpses,” says CollPlant CEO Yehiel Tal, noting that the US Food and Drug Administration (FDA) and other international health regulatory agencies have expressed serious safety concerns with respect to the use of both animal and human corpse tissues.
CollPlant’s plant-derived collagen poses no safety risks and can be considered a green technology, eliminating the industrial waste and ecological damage associated with the raising of livestock. In addition, the company is providing tobacco farmers with a healthier and more lucrative use for their crops.
“The leaves of a single tobacco plant can yield about 100 grams of tobacco (for cigarettes) or about a gram of genetically-engineered human collagen,” says Prof. Oded Shoseyov, CollPlant’s co-founder and the inventor of the technology. “And from a single gram of collagen it is possible to produce, for example, about three injections of highly-valuable wound healing gel for patients suffering from diabetic ulcers.”
In developing CollPlant’s innovative technology, Shoseyov had to overcome a formidable scientific challenge. “Most proteins in the body are the result of a single gene but there are five different genes responsible for the production of collagen.”
Shoseyov’s success in transferring all five genes into a transgenic plant that could produce collagen was acknowledged earlier this year when he was awarded the prestigious Hebrew University Kaye Innovation Award for “scientific excellence with commercial potential.”
Good news from the FDA
CollPlant is well on the way to leveraging the commercial potential of Shoseyov’s invention. The company has begun to market collagen as a raw material to Japanese manufacturers and in August received good news from the FDA about its first product.
“The FDA informed us that they have agreed to classify our Vergenix wound dressing as a medical device, rather than as a drug or biologic product,” says Tal. “This is a breakthrough because the medical device regulatory review process is much simpler and quicker than that used for products defined as drugs or biologics.”
Vergenix is just the first of several regenerative tissue products in the CollPlant pipeline that target the multi-billion dollar wound management market. These products include gel formulations for deep-tunneled wounds associated with diabetic ulcers, as well as wound dressings for acute and chronic wounds.
Other CollPlant products will attempt to meet the growing demand for collagen-based orthopedic products. In the US alone, each year there are about 800,000 ligament and tendon repair procedures, 400,000 shoulder operations and more than 500,000 bone graft procedures, all of which require collagen.
CollPlant has received strong support from leading investors since its inception. Investment funds headed by two prominent healthcare industrialists, former Teva Pharmaceuticals CEO Eli Hurvitz and Perrigo founder Mory Arkin, were among the founding investors. Earlier this year the company began to trade publicly on the Tel Aviv Stock Exchange.
Tuesday, October 12, 2010
Invasive shrub increases risk of human disease
There are many ways of fighting disease, but Brian Allan from Washington University has suggested a most unusual one – a spot of weeding. Allan’s research shows that getting rid of a plant called the Amur honeysuckle might be one of the best ways of controlling an emerging human disease called ehrlichiosis. The plant, however, doesn’t cause the disease. The connection between the two is far more complicated than that.
The Amur honeysuckle is an Asian plant that’s naturally alien to American shores. But, like many species that are brought to new habitats, it has become an invader. It forms thick growths that deprive native plants of light, causing local diversity to plummet in the face of an expanding blanket of honeysuckle. This story has been repeated all over the world with different species cast as invasive villains, and different communities cast as suffering victims. But the true consequences of these invasions often go unnoticed.
The honeysuckle doesn’t just crowd out local plants; Allan has found that it also attracts white-tailed deer. Where the deer go, so do their parasites, and these include the lone star tick, the animal that spreads ehrlichiosis. Through their blood-sucking bites, the ticks spread five species of bacteria that infect and kill white blood cells. This weakens the immune systems of their hosts and causing the flu-like symptoms that accompany a bout of ehrlichiosis.
More honeysuckle means more deer, which means more ticks, which means more bacteria, which means more potentially infected humans. This invasive shrub might help to explain why cases of ehrlichiosis have gone up by around 6 times in the early part of the 21st century. In 1999, the Centers for Disease Control and Prevention recorded just 100 or so cases of ehrlichiosis in the United States. By 2006, that number had risen to just under 600.
Allan discovered this remarkable chain of events by carrying out a series of field surveys in the Missouri woodlands. He found that compared to honeysuckle-free areas, invaded zones had 18 times as much plant matter and around five times as many deer (which presumably are drawn to areas with more shelter and potential food). As a result, they also had 10 times as many ticks that were infected by ehrlichiosis-causing bacteria. Clearly, the risk of catching the disease is higher in areas that contain honeysuckle.
To test his hypothesis, Allan removed the honeysuckle from selected patches of woodland. The result: far fewer signs of deer and far fewer infected ticks. Allan also found that the presence of honeysuckle didn’t affect the odds of a tick being infected with the problematic bacteria, or their odds of survival. This suggests that the removal of the honeysuckle was indeed lowering the numbers of ticks by driving away the deer, rather than simply creating conditions that are more hostile towards ticks.
This is a good example of an invasive species increasing the burden of human disease and it’s unlikely to be the only one. Other studies have found that in the northeastern United States, the honeysuckle and the Japanese barberry (another invasive shrub) might increase the risk of Lyme disease, another tick-borne bacterial disease.
To Allan, these domino effects mean that removing invasive species isn’t just an environmental cause – it’s a public health issue too. Honeysuckle might repress local plants but through a convoluted chain of events, it could end up repressing the immune systems of local people. That should provide even more incentive to deal with these invaders. As Allan himself writes,
“Our finding that removal of the invader mitigates disease risk, coupled with the benefits of invasive plant removal to wildlife communities, suggests a potential “win-win” scenario for biodiversity conservation and human health.”
The Amur honeysuckle is an Asian plant that’s naturally alien to American shores. But, like many species that are brought to new habitats, it has become an invader. It forms thick growths that deprive native plants of light, causing local diversity to plummet in the face of an expanding blanket of honeysuckle. This story has been repeated all over the world with different species cast as invasive villains, and different communities cast as suffering victims. But the true consequences of these invasions often go unnoticed.
The honeysuckle doesn’t just crowd out local plants; Allan has found that it also attracts white-tailed deer. Where the deer go, so do their parasites, and these include the lone star tick, the animal that spreads ehrlichiosis. Through their blood-sucking bites, the ticks spread five species of bacteria that infect and kill white blood cells. This weakens the immune systems of their hosts and causing the flu-like symptoms that accompany a bout of ehrlichiosis.
More honeysuckle means more deer, which means more ticks, which means more bacteria, which means more potentially infected humans. This invasive shrub might help to explain why cases of ehrlichiosis have gone up by around 6 times in the early part of the 21st century. In 1999, the Centers for Disease Control and Prevention recorded just 100 or so cases of ehrlichiosis in the United States. By 2006, that number had risen to just under 600.
Allan discovered this remarkable chain of events by carrying out a series of field surveys in the Missouri woodlands. He found that compared to honeysuckle-free areas, invaded zones had 18 times as much plant matter and around five times as many deer (which presumably are drawn to areas with more shelter and potential food). As a result, they also had 10 times as many ticks that were infected by ehrlichiosis-causing bacteria. Clearly, the risk of catching the disease is higher in areas that contain honeysuckle.
To test his hypothesis, Allan removed the honeysuckle from selected patches of woodland. The result: far fewer signs of deer and far fewer infected ticks. Allan also found that the presence of honeysuckle didn’t affect the odds of a tick being infected with the problematic bacteria, or their odds of survival. This suggests that the removal of the honeysuckle was indeed lowering the numbers of ticks by driving away the deer, rather than simply creating conditions that are more hostile towards ticks.
This is a good example of an invasive species increasing the burden of human disease and it’s unlikely to be the only one. Other studies have found that in the northeastern United States, the honeysuckle and the Japanese barberry (another invasive shrub) might increase the risk of Lyme disease, another tick-borne bacterial disease.
To Allan, these domino effects mean that removing invasive species isn’t just an environmental cause – it’s a public health issue too. Honeysuckle might repress local plants but through a convoluted chain of events, it could end up repressing the immune systems of local people. That should provide even more incentive to deal with these invaders. As Allan himself writes,
“Our finding that removal of the invader mitigates disease risk, coupled with the benefits of invasive plant removal to wildlife communities, suggests a potential “win-win” scenario for biodiversity conservation and human health.”
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