Thursday, February 16, 2017

Podcast: Contacting Congress, 21st Century Cures, & Antibiotics

By: Ian McLaughlin & Liana Vaccari






Antibiotic resistance, policy and prevention
By: Liana Vaccari

What are antibiotics? Antibiotics, which might also be called antimicrobial or antibacterial agents, are chemicals that can disrupt the life-cycle of bacteria in a few different ways; some actively kill the cells, others prevent them from reproducing, and others inhibit their ability to metabolize energy sources.  Over the years, they’ve been used for everything from strep throat to pneumonia1, but use has recently been dialed back because bacteria are becoming resistant to antibiotics that currently exist. One reason this has become an issue is that discoveries of new antibiotics can’t keep pace with the ability of the bacteria to resist old ones because developing new drugs is a long and expensive process.2,3
Early this year, a woman died of an infection caused by a strain of bacteria that none of the 26 antibiotics available in America could clear.4 This is pretty unusual and alarming – even if no one else is infected with the same exact strain here, the appearance of this superbug is a reminder that the antibiotics we have are vulnerable.
But how do the bacteria become resistant in the first place?3 When someone develops a bacterial infection, it’s because a strain of bacteria that can produce toxins that breakdown tissues or cause an immunological response that can be harmful (e.g. mucus build up) has set up camp in his or her body.5 The bacteria can then start doubling over relatively short times, quickly reaching thousands or millions of cells. When bacteria multiply, they basically copy genetic code from the parent cells to the next generation, but it isn’t always perfect. This is almost like when you tell stories from one generation to another, or play the game telephone. Little details get changed each time it’s told. When this happens in genes, this is called mutating, and no mutation is exactly the same from bacterium to bacterium. Mutations sometimes have no noticeable effect. Sometimes it changes in a way that renders the antibiotic less effective – maybe the cell wall is stronger and less likely to be damaged by that particular antibiotic, or maybe it had a slight change in the way the metabolism functions which is no longer as dependent on the process that was hindered by antibiotics. Some bacteria also resist death by antibiotics by producing biofilms that physically prevents antibiotics from reaching the cells. Others create enzymes that can break down the antibiotic, and others can even selectively pump out the antibiotic from inside the cell.
With thousands to millions of copies being made by the bacteria, there will inevitably be some mutants, even if not many, that are able to resist the effects of the antibiotics by one of those means. Sometimes, your infection might be cleared for the most part, with the help of both antibiotics and your own immune response, but if even a couple of these bacteria survive that were not affected by the antibiotics, now resistant to that drug, they can begin to multiply all over again until there are enough to cause a significant infection once more. You might not be as susceptible to this infection because your immune system has learned how to attack these in particular, but some of the bacteria will inevitably spread through the population and now be more resistant to the type of the antibiotic you used.
In the short term, it is to your benefit to use antibiotics right away when you have a bacterial infection. It could quickly clear your infection and return you to full health. But in doing so, you may have been host to bacteria evolving to resist that now will spread through the population, and the cheap, readily available antibiotic that you used is now less effective for other people. At some point, a doctor may have to prescribe stronger and stronger antibiotics to combat the continually mutating and proliferating bacteria which gives rise to the kind of superbug that killed the woman in Nevada. This is dangerous for you as well because in the long run, overreliance on antibiotics can make it harder for everyone to fight off infections.
This is such an issue that it has been made a priority on a national and global level. Both the World Health Organization6 and the Center for Disease Control7 are working to:
  • Prevent infections,
  • Increase awareness of antibiotic resistance and stewardship of antibiotics,
  • Track infections that do occur, and
  • Develop new drugs, diagnostics, and interventions
So what can you do to decrease the likelihood of antibiotic resistant bacteria in your own life?1-3,8-11
  • Antibiotics don’t work on viral infections which cause common colds, flu, and the typical sore throat. Strep throat is a bacterial infection that doctors test for when they swab your throat. The CDC believes that at least 30% of the time12, antibiotics are prescribed unnecessarily or inappropriately; people have used them for infections they may have been able to recover from without the drugs and in some cases, antibiotics are prescribed when they would have no effect. If you are going to take antibiotics, make sure what you have is actually a bacterial infection.
  •  If you do have a bacterial infection, take the full course of antibiotics that you are prescribed. The earlier the mutant bacteria are exposed to the antibiotics, the more likely they are to still respond, and the timeline and doses are carefully designed to kill as many as possible, even if your noticeable symptoms are gone. The earlier you stop taking the medication, the larger the population of bacteria that survives the first does.
  • On a day-to-day basis, don’t use antibacterial or antimicrobial soaps. According to the FDA, antibacterial soap is no more likely to prevent infections than regular soap, and the antibacterial additives also contribute to antibiotic resistance. This is not relevant with alcohol based hand sanitizers, but generally speaking, regularly washing your hands with normal soap and water is sufficient and effective at preventing infections otherwise spread by contact.
With these measures in mind, hopefully this appearance by a superbug in Nevada will be an isolated incident.

References:
1         Medical News Today, Antibiotics (2 January 2017), http://www.medicalnewstoday.com/articles/10278.php
3         Center for Disease Control, Drug Resistance (5 January 2017), https://www.cdc.gov/drugresistance/
4         Center for Disease Control Morbidity and Mortality Weekly Report (13 January 2017), https://www.cdc.gov/mmwr/volumes/66/wr/mm6601a7.htm?s_cid=mm6601a7_w
5         Medline Plus, Bacterial Infections (17 January 2017), https://medlineplus.gov/bacterialinfections.html
6         World Health Organization, Antimicrobial resistance (n-d), Retrieved on 15 December 2016, http://www.who.int/antimicrobial-resistance/global-action-plan/en/
7         Center for Disease Control, CDC Role (16 September 2013), https://www.cdc.gov/drugresistance/cdc_role.html
8         Medline Plus, Antibiotics (2 January 2017), https://medlineplus.gov/antibiotics.html
9         Center for Disease Control, Get Smart (14 November 2016), https://www.cdc.gov/features/getsmart/
11     Alliance for the Prudent Use of Antibiotics (n-d), Retrieved on 15 December 2016, http://emerald.tufts.edu/med/apua/about_issue/when_how.shtml
12     Center for Disease Control, Press Release (3 May 2016), https://www.cdc.gov/media/releases/2016/p0503-unnecessary-prescriptions.html

Tuesday, December 20, 2016

Event Recap: Intellectual Property Panel “From Research to Patent”


by Adrian Rivera-Reyes

On November 10th, the Penn Science Policy Group and the Penn Intellectual Property Group at Penn Law co-hosted a panel discussion focused on intellectual property and how to patent scientific research. The panel included Peter Cicala, Chief Patent Counsel at Celgene Corp.; Dr. Dora Mitchell, Director of the UPstart Program at the Penn Center for Innovation (PCI) Ventures; and Dr. Michael C. Milone, Assistant Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania (HUP), and Assistant Professor of Cell and Molecular Biology at Penn Medicine.

The event started with the introduction of both groups by their respective presidents and was proceeded by Kimberly Li giving an introduction of the panelists. Next, Peter gave a short PowerPoint presentation with a general introduction of intellectual property. Below are some key points to understand intellectual property/patent law 1,2:

1) In general, patents provide a “limited monopoly” that excludes others from making an invention, using, offering for sale, selling, or otherwise practicing an invention, but it does not confer upon the patentee a right to use the said invention. Thus, patents serve as a form of protection for the owner.
2) A single invention can only be patented once; once the patent on that invention expires, others may not file to patent the same invention again.
3) In order to confer a patent, the United States Patent and Trademark Office ensures that inventions of patentable subject matter meet the following legal requirements: i) inventions must be novel, ii) inventions must be useful, and iii) inventions must be non-obvious.
4) Utility patents only last for 20 years from the date of filing. After 20 years, anyone can make, use, offer for sale, sell, or practice the invention. A single invention cannot be re-patented after the time is done. In contrast, trademarks or trade secrets last forever, and copyrights last for the lifetime of the author.  
5) The United States Patent and Trademark Office follows the ‘first to file’ rule. Thus, the first person or entity to file a patent is the assumed owner.
6) Patents can be invalidated by the United States Patent and Trademark Office.

A clever example discussed by Peter Cicala was the patenting of a new car feature. If X company has submitted and received a patent for a car and Y company makes a new feature for the car, they can patent the new feature (as long as it meets the legal requirements introduced above). Once the patent for the new feature is conferred to Y company then they can produce that one feature, but not the car that was patented by X company, unless a license is provided by X company to Y company. Thus, the patent for Y company only gives them the power to prevent others from making that new feature.

Conferring Patents in the US and Internationally

First, there has to be an invention of some sort. Once there is an invention, a patent is filed. Patents are drafted free-hand, unlike a tax application where one has a specific form to fill. For patents, one has to start from scratch. Patents are usually long (some can reach 500 pages in length) and there are many legal requirements on what to say in the application and how to say it. Eventually, when one files a patent application it will go to the patent office. A patent examiner will, as the name suggests, examine it and deliberate with the patent office over the course of 3-5 years as they point out sections that need further editing, clarification, or justification. There is a lot of back and forth, until the examiner agrees that the invention has satisfied the patent requirements. Then, one pays fees and the patent is awarded. Fun fact: In the US, patents are granted only on Tuesdays.

On a global basis, one files a single international patent and the designated patent offices around the world examine it locally. If an office grants a patent, such patent will only be valid in that jurisdiction. That is why submitting patents cost so much, because one files and pays legal fees for each jurisdiction. For example, if a patent is filed in Japan for a compound, a different entity can manufacture the compound freely in the US, but not in Japan. This is one reason why companies and universities are very careful when filing patents.

Intellectual Property in Industry

Pharmaceutical products start with a great idea, but for every product in the market there are about 10,000 that fail. Therefore, companies file many patents even though many of those patents may not have any commercial value in 5-6 years. It costs about $500K to file (including filing and attorneys’ fees) and receive a single issued patent, which means companies spend a lot in patents (i.e. 10,000 patent submissions each worth $500K)! Out of those 10,000 patents, typically one will make the company about an estimated $5 billion a year in returns.

A student asked, “Is submitting a patent the same price for a university as it is for a company?” In essence, no! The patent office makes a distinction between large and small entities. Small entities, based on requirements provided by the patent office3, pay half the fees, but attorneys charge a fixed price. In the end, small entities save just a small percentage of money. Another question asked by an audience member was “what is patentable in the pharma business?” If one patents a molecule, no one else can infringe or use that molecule itself. That is how companies patent drugs or their associated components. One can also patent dosing regimens, formulations, modes of administration, etc. The compound claim gives the most protection, because it is very hard to make a knock-off of a molecule.

Intellectual Property in Academia

A student raised the issue that there is a lot of communication that occurs in science, especially at conferences, symposia, or amongst colleagues, classmates, etc. That seems to be a big risk in the context of protecting one's intellectual property, but doing so is an unavoidable risk when one does scientific research.

Dora, patent analyst from PCI Ventures, then proceeded to discuss the issues brought up from an academic perspective. She said, “The question raised here is that when one works in an academic institution the work is knowledge based and disseminated to others.... How does one draw the line from all that to protect something valuable?” What most, if not all, academic/research institution do is have their lawyers work very closely with faculty, so that anytime they are about to publish a paper, go to a conference, attend grand rounds, or any other such public appearance, the lawyers will hustle and get an application submitted before such events.

In addition to these more public forums, problems can arise from talking with friends who are not directly associated with the work. An example of this pertains to OPDIVO®, a drug patented by Ono Pharmaceuticals and the Kyoto University in the 90’s, which later was exclusively licensed to Bristol-Myers Squibb who launched the drug. Recently, Dana Farber Cancer Institute sued Ono Pharmaceuticals and Bristol-Myers Squibb because the principal investigator at Kyoto University had periodically consulted a colleague at Dana Farber for his advice. The professor-consultant at Dana Farber would send some data he thought was helpful and consult with them. Dana Farber sued both companies, claiming that the now-retired professor from its institution should be included as an inventor in the patent. Because an inventor of a patent is part-owner, Dana Farber is actually claiming ownership of the patent and will receive compensation from the sales of products under the patent4,5.

Michael, Penn Med professor who works intimately with a team of lawyers from PCI because he regularly files patents, said that balancing confidentiality with science communication is a difficult task. He commented, “I think it comes down to how important one thinks the invention is and a lot of the times the patent will not get developed if it will not bring any money to the owner (company/institution).” Moreover, there has to be a conversation with the university because the university pays for the patent, so it decides what to file. It also depends on the resources of the university. Regarding the work of graduate students or postdoctoral fellows, there are more considerations. Students and postdocs want and need to publish, go to conferences, and present their work in order to move forward with their careers; thus patents can be a rather limiting step for them.

From the industry perspective, Peter clarified that the rule at Celgene is that no one can talk about anything until the patent application is filed. Once the patent application is filed, employees are free to talk to whomever they wish without causing a situation like the one with Dana Farber and Bristol-Myers Squibb, since the patent application has been filed prior to any communication.

Thus, a clear difference between industry and academia is that in industry, things are kept under wraps and then a patent is filed, whereas in academia patents are filed early to make sure that the institution does not lose the rights of patenting by making the information public. Because universities file very early, there is a lot to deal with afterwards. The costs of prosecution are high, and sometimes the application does not make it through the full process, because universities cannot afford to throw $500K for an application if they are not confident on getting a return on the investment. The reason to file for some universities might be purely strategic.

Ownership vs. Inventorship

Another interesting topic discussed, was that of ownership vs. inventorship. There is the notion that ownership follows inventorship. In most cases, people do not file patents on their own; they work for companies or universities. Usually, an employment contract will state that if an employee invents something while employed by that entity, then ownership to a resultant patent will be assigned to the employer. Thus, the person is the inventor but not the owner of the patent; the entity is the owner. For academic research, the Bayh-Dole act was enacted to allow universities to own inventions that came from investigations funded by the federal government6. Dora explained that, “Government officials got together and agreed that they awarded so much money into research and good stuff came out of it, which the government would own but not file patents or do anything with it commercially."

A preliminary list of inventors is written when the patent is filed, but legally the inventors are the people that can point to a claim and say: "I thought of that one." Inventors have to swear under oath that they thought of a particular claim, and need to be able to present their notebooks with the data supporting a claim of inventorship. Inventors are undivided part-owners of the patent, which means that any inventor listed in the patent can license that patent in any way, without accounting for any of the other inventors. Additionally, there is a difference between the people that think about the claims and the people that actually execute the subject matter of the resulting claim. If a person is only executing experiments without contributing intellectually to the idea or procedure, then that person is not an inventor. For those in academic research, this often differs from how paper authorship is decided – usually performing an experiment is sufficient.

Summary

The discussion prompted the researchers in the room to be on the lookout for ideas they have that can result in patents, and to be careful when discussing data and results with people outside of their own research laboratory. Also, the discussion exposed key differences between intellectual property lawyers working for universities and industries, as opposed to law firms that have departments working on intellectual property. Ultimately, students felt they gained a basic understanding on how intellectual property works, the rules to file patents, and some intrinsic differences between academic and industry research.

References:

1) United States Patent and Trademark Office – (n.d.) Retrieved December 11, 2016 from https://www.uspto.gov/patents-getting-started/general-information-concerning-patents
2) BITLAW – (n.d.) Retrieved December 11, 2016 from http://www.bitlaw.com/patent/requirements.html
3) United States Patent and Trademark Office – (n.d.) Retrieved December 20, 2016 from https://www.uspto.gov/web/offices/pac/mpep/s2550.html
4) Bloomberg BNA – (2015, October 2) Retrieved December 11, 2016 FROM https://www.bna.com/dana-farber-says-n57982059025/
5) United States District Court (District Court of Massachusetts). http://www.dana-farber.org/uploadedFiles/Library/newsroom/news-releases/2015/dana-farber-inventorship-complaint.pdf
6) National Institute of Health, Office of Extramural Research – (2013, July 1) Retrieved December 11, 2016 from https://grants.nih.gov/grants/bayh-dole.htm

Tuesday, November 29, 2016

Event Recap: Anonymous Peer Review & PubPeer

by Ian McLaughlin 

On the 24th of October, the Penn Science Policy Group met to discuss the implications of a new mechanism by which individuals can essentially take part in the peer review process.  The group discussion focused on a particular platform, PubPeer.com, which emerged in 2012 and has since become a topic of interest and controversy among the scientific community.  In essence, PubPeer is an online forum that focuses on enabling post-publication commentary, which ranges from small concerns by motivated article readers, to deeper dives into the legitimacy of figures, data, and statistics in the publication.  Given the current state of the widely criticized peer-review process, we considered the advantages and disadvantages of democratizing the process with the added layer of anonymity applied to reviewers.

PubPeer has been involved in fostering investigations of several scandals in science.  Some examples include a critical evaluation of papers published in Nature 2014 entitled Stimulus-triggered fate conversion of somatic cells into pluripotency [1].  The paper described a novel mechanism by which pluripotency might be induced by manipulating the pH environments of somatic cells.  However, following publication, concerns regarding the scientific integrity of published experiments were raised, resulting in the retraction of both papers and an institutional investigation.
  
Subsequently, the publications of a prolific cancer researcher received attention on PubPeer, ultimately resulting in the rescission of a prestigious position at a new institution eleven days before the start date due, at least in part, to PubPeer commenters contacting faculty at the institution.  When trying to return the professor’s former position, it was no longer available.  The professor then sued PubPeer commenters, arguing that the site must identify the commenters that have prevented a continued career in science.  PubPeer, advised by lawyers from the ACLU working pro-bono, is refusing to comply – and enjoy the support of both Google and Twitter, both of which have filed a court brief in defense of the website [2]. 
                  
Arguably at its best, PubPeer ostensibly fulfills an unmet, or poorly-met, need in the science publication process.  Our discussion group felt that the goal of PubPeer is one that the peer review process is meant to pursue, but occasionally falls short of accomplishing. While increased vigilance is welcome, and bad science – or intentionally misleading figures – should certainly not be published, perhaps the popularity and activity on PubPeer reveals a correctable problem in the review process rather than a fundamental flaw. While the discussion group didn’t focus specifically on problems with the current peer review process – a topic deserving its own discussion [3] – the group felt that there were opportunities to improve the process, and was ambivalent that a platform like PubPeer is sufficiently moderated, vetted, and transparent in the right ways to be an optimal means to this end.
                  
Some ideas proposed by discussion participants were to make the peer-review process more transparent, with increased visibility applied to the reasons a manuscript is or is not published.  Additionally, peer-review often relies upon the input of just a handful of volunteer experts, all of whom are frequently under time constraints that can jeopardize their abilities to thoroughly evaluate manuscripts – occasionally resulting in the assignment of peer review to members of related, though not optimally relevant, fields [4].  Some discussion participants highlighted that a democratized review process, similar to that of PubPeer, may indeed alleviate some of these problems with the requirement that commenters be moderated to ensure they have relevant expertise.  Alternatively, some discussion participants argued, given the role of gate-keeper played by journals, often determining the career trajectories of aspiring scientists, the onus is on Journals’ editorial staffs to render peer review more effective.  Finally, another concept discussed was to layer a 3rd party moderation mechanism on top of a platform like PubPeer, ensuring comments are objective, constructive, and unbiased.
                  
The concept of a more open peer review is one that many scientists are beginning to seriously consider.  In Nature News, Ewen Callaway reported that 60% of the authors in Nature Communications agreed to have publication reviews published [7].  However, while a majority of responders to a survey funded by the European Commission believed that open peer review ought to become more routine, not all strategies of open peer review received equivalent support.

[7]

                  
Ultimately, the group unanimously felt that the popularity of PubPeer ought to be a signal to the scientific community that something is wrong with the publication process that requires our attention with potentially destructive ramifications [5].  Every time a significantly flawed article is published, damage is done to the perception of science and the scientific community, and at a time when the scientific community still enjoys broadly positive public perception [6], now is likely an opportune time to reconsider the peer-review process – and perhaps learn some lessons that an anonymous post-publication website like PubPeer might teach us.

References


1) PubPeer - Stimulus-triggered fate conversion of somatic cells into pluripotency. (n.d.). Retrieved November 25, 2016, from https://pubpeer.com/publications/8B755710BADFE6FB0A848A44B70F7D 

2) Brief of Amici Curiae Google Inc. and Twitter Inc. in Support of PubPeer, LLC. (Michigan Court of Appeals). https://pubpeer.com/Google_Twitter_Brief.pdf

3) Balietti, S. (2016). Science Is Suffering Because of Peer Review’s Big Problems. Retrieved November 25, 2016, from https://newrepublic.com/article/135921/science-suffering-peer-reviews-big-problems

4)Arns M. Open access is tiring out peer reviewers. Nature. 2014 Nov 27;515(7528):467. doi: 10.1038/515467a. PubMed PMID: 25428463.

5) Jha, Alok. (2012). False positives: Fraud and misconduct are threatening scientific research. Retrieved November 25, 2016, from https://www.theguardian.com/science/2012/sep/13/scientific-research-fraud-bad-practice

6) Hayden, E. C. (2015, January 29). Survey finds US public still supports science. Retrieved November 25, 2016, from http://www.nature.com/news/survey-finds-us-public-still-supports-science-1.16818 

7) Callaway E. Open peer review finds more takers. Nature. 2016 Nov 10;539(7629):343. doi: 10.1038/nature.2016.20969. PubMed PMID: 27853233

Sunday, November 6, 2016

Tracing the ancestry and migration of HIV/AIDS in America

by Arpita Myles
Acquired immunodeficiency syndrome or AIDS is a global health problem that has terrified and intrigued scientists and laypeople alike for decades. AIDS is caused by the Human Immunodeficiency Virus, or HIV, which is transmitted through blood, semen, vaginal fluid, and from an infected mother to her child [1]. Infection leads to failure of the immune system, increasing susceptibility to secondary infections and cancer, which are mostly fatal. Considerable efforts are being put into developing prophylactic and therapeutic approaches to tackle HIV-AIDS, but there is also interest in understanding how the disease became so wide-spread. With the advent of the Ebola and Zika viruses in the last couple of years, there is a renewed urgency in understanding the emergence and spread of viruses in the past in order to prevent those in the future. The narrative surrounding the spread of HIV has been somewhat convoluted, but a new paper in Nature by Worobey et. al, hopes to set the record straight [2].
Humans are supposed to have acquired HIV from African chimpanzees- presumably as a result of hunters coming in contact with infected blood, containing a variant of the virus that had adapted to infect humans. The earliest known case of HIV in humans was detected in 1959 in Kinshasa, Democratic Republic of the Congo, but the specific mode of transmission was never ascertained [3].
There has been little or no information about how HIV spread to United States, until now. HIV incidences were first reported in the US in 1981, leading to the recognition of AIDS [4]. Since the virus can persist for a decade or more prior to manifestation of symptoms, it is possible that it arrived in the region long before 1981. However, since most samples from AIDS patients were collected after this date, efforts to establish a timeline for HIV’s entry into the states met with little success. Now, researchers have attempted to trace the spread of HIV by comparing genetic sequences of contemporary HIV strains with blood samples from HIV patients dating back to the late 1970’s [2]. These samples were initially collected for a study pertaining to Hepatitis B, but some were found to be HIV seropositive. This is the first comprehensive genetic study of the HIV virus in samples collected prior to 1981.
The technical accomplishment of this work is significant as well. In order to circumvent the problems of low amounts and extensive degradation of the viral RNA from the patient samples, they developed a technique they call “RNA jackhammering.”  In essence, a patient’s genome is broken down into small bits and overlapping sequences of viral RNA are amplified. This enables them to “piece together” the viral genome, which they can then subject to phylogenetic analysis.
Using novel statistical analysis methods, Worobey et al. reveal that the virus had probably entered New York from Africa (Haiti) during the 1970s, whereupon it spread to San Francisco and other regions. Upon analyzing the older samples, the researchers found that despite bearing similarities with the Caribbean strain, the strains from San Francisco and New York samples differed amongst themselves. This suggests that the virus had entered the US multiple, discreet times and then began circulating and mutating. Questions still remain regarding the route of transmission of the virus from Haiti to New York.
The relevance of this study is manifold. Based on the data, one can attempt to understand how pathogens spread from one population to another and how viruses mutate and evolve to escape natural immunity and engineered therapeutics. Their molecular and analytical techniques can be applied to other diseases and provide valuable information for clinicians and epidemiologists alike. Perhaps the most startling revelation of this study is that contemporary HIV strains are more closely related to their ancestors than to each other. This implies that information derived from ancestral strains could lead to development of successful vaccine strategies.
Beyond the clinic and research labs, there are societal lessons to be learned as well. Published in 1984, a study by CDC (Center for Disease Control) researcher William Darrow and colleagues traced the initial spread of HIV in the US to GaĆ©tan Dugas- a French Canadian air steward. Examination of Dugas’s case provided evidence linking HIV transmission with sexual activity. Researchers labeled Dugas as “Patient O”, as in “Out of California” [5]. This was misinterpreted as “Patient Zero” by the media- a term still used in the context of other epidemics like flu and Ebola. The dark side of this story is that Dugas was demonized in the public domain as the one who brought HIV to the US. As our understanding of the disease and its spread broadened, scientists and historians began to discredit the notion that Dugas played a significant role. However, scientific facts were buried beneath layers of sensationalism and hearsay and the stigma remained.
Now, with the new information brought to light by Worobey’s group, Dugas’s name has been cleared. Phylogenetic analysis of Dugas’s strain of HIV was sufficiently different from the ancestral ones, negating the possibility that he initiated the epidemic.
The saga in its entirety highlights the moral dilemma of epidemiological studies and the extent to which the findings should be made public. Biological systems are complicated, and while narrowing down origin of a disease has significance clinical relevance, we often fail to consider collateral damage. The tale of tracking the spread of HIV is a cautionary one; scientific and social efforts should be focused more on resolution and management, rather than on vilifying unsuspecting individuals for “causing” an outbreak.

References:
1. Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet. 2014 Jul 19;384(9939):258-71.
2. Worobey M, Watts TD, McKay RA et al., 1970s and 'Patient 0' HIV-1 genomes illuminate early HIV/AIDS history in North America. Nature. 2016 Oct 26. doi: 10.1038/nature19827.
3. Faria NR, Rambaut A et al., HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations. Science. 2014 Oct 3;346(6205):56-61.
4. Centers for Disease Control (CDC). Pneumocystis pneumonia--Los Angeles. MMWR Morb Mortal Wkly Rep. 1981 Jun 5;30(21):250-2.
5. McKay RA. “Patient Zero”: The Absence of a Patient’s View of the Early North American AIDS Epidemic. Bull Hist Med. 2014 Spring: 161-194.