Inspiring the Next Generation of Scientists – A Conversation with Dr. Susan K. Whoriskey – by Erika Kurt, Small World Initiative

DR. SUSAN K. WHORISKEY (CENTER) WITH DR. NICHOLE BRODERICK (LEFT) – ASSISTANT PROFESSOR OF MOLECULAR AND CELL BIOLOGY AT THE UNIVERSITY OF CONNECTICUT – AND ERIKA KURT (RIGHT) – SMALL WORLD INITIATIVE PRESIDENT & CEO – AT SWI'S ANNUAL SYMPOSIUM AT ASM MICROBE IN BOSTON IN JUNE. (MEAGAN MOORE PHOTO) DR. SUSAN K. WHORISKEY (CENTER) WITH DR. NICHOLE BRODERICK (LEFT) – ASSISTANT PROFESSOR OF MOLECULAR AND CELL BIOLOGY AT THE UNIVERSITY OF CONNECTICUT – AND ERIKA KURT (RIGHT) – SMALL WORLD INITIATIVE PRESIDENT & CEO – AT SWI’S ANNUAL SYMPOSIUM AT ASM MICROBE IN BOSTON IN JUNE. (MEAGAN MOORE PHOTO)

by Erika Kurt

On Saturday, June 18th, Erika Kurt, President and CEO of the Small World Initiative (SWI), sat down with biotechnology entrepreneur Dr. Susan K. Whoriskey, PhD, a leader in the biotech industry, at SWI’s 3rd Annual Symposium held at ASM Microbe in Boston. Whoriskey was a member of the Founding Executive Teams of four Boston biotechs: Cubist Pharmaceuticals, Momenta, Moderna, and PNA Innovations. At Cubist, Whoriskey was a member of the team that was instrumental in developing and bringing to the market Cubicin (daptomycin), a lipopeptide antibiotic active against drug-resistant bacteria, in 2003. Whoriskey shared some tales from the lab bench, the boardroom, and her inspirational scientific career.

DR. SUSAN K. WHORISKEY
DR. SUSAN K. WHORISKEY

On July 18th, I had the opportunity to sit down with Dr. Susan K. Whoriskey to share her inspiring story with Small World Initiative students and faculty. Throughout her career, Whoriskey has been creating companies that pioneer scientific breakthroughs to save lives and improve healthcare costs as a member of the founding Executive Teams of three of Massachusetts top successful biotech companies and a recently started fourth venture. In her roles, she has been instrumental in helping bring three lifesaving drugs to the market as well as others that are currently in clinic trials. Of particular note, she shared in detail her involvement with the antibiotic Cubicin (daptomycin), one of the first new chemical classes of antibiotics approved by the Food and Drug Administration (FDA) in over 50 years. Whoriskey has been a Research Fellow in Molecular Genetics at Harvard Medical School with 2009 Nobel Prize recipient Dr. Jack Szostak, a consultant to venture capital firm Polaris Venture Partners, and an Entrepreneur in Residence at the Massachusetts Institute of Technology. She earned a Bachelor of Science in Microbiology from the University of Massachusetts-Amherst and a PhD in Molecular Biology from the Molecular Biology Institute at the University of California, Los Angeles (UCLA).

The Power of Science

As a very young girl, Whoriskey was drawn to science. Her mother passed away from cancer when she was just seven, and she intimately learned how dramatically ill health could have a lasting impact on a family and a life. Yet, she also saw how science could change that through medicine. Whoriskey’s father was a naval surgeon during World War II and later practiced as a pediatrician. During his medical career, his practice transformed from providing palliative care to dying patients to saving patients lives thanks to the “miracle drugs” of antibiotics and the polio vaccine. According to Whoriskey, “The way my father talked about how his medical practice transformed in his lifetime deeply impacted me and elucidated the power of science and the hopefulness that it brings to the world.”

Whoriskey decided that she wanted to be a part of that story, in some way big or small.

The Impact of Engaging Science Courses

However, due to gender stereotypes, the scientific community almost missed out on Whoriskey’s contributions. When Whoriskey got to the University of Massachusetts-Amherst, she initially thought that science “would be too hard” and “was for the guys.” She declared a major in journalism having been inspired by Bob Woodward and Carl Berstein’s All the President’s Men. Luckily, her school had mandatory distribution requirements. After having delayed taking her science requirement until the second semester of her junior year, she took a science course for non-science majors, The Microbiology of Cancer, taught by an engaging and communicative genetics professor. This professor exuded the joy and adventure of science, and Whoriskey tapped into something in herself “that had been percolating” and did an about-face. With this new motivation and drive, Whoriskey was able to complete all of her microbiology requirements during her senior year.

The Choice

After graduating from college in 1981 with a degree in microbiology, Whoriskey entered the job market during a recession. Following weeks of radio silence on her job applications, she finally landed two interviews on the same day. One job was with a professor working in a clinical microbiology lab and required repeating the same test every day following a standardized testing protocol, and the second job involved working with a professor at Harvard doing exploratory research on cholera to understand the mechanism of action of the toxin agent causing the disease.

These opposing opportunities gave Whoriskey the chance to evaluate her own interests, and in considering the job choice, she discovered she was an entrepreneur at the end of the day. She went for the research position, fraught with ambiguity and uncertainty but none the less invigorated by the challenge, even though it paid less than the other option. She worked there for two years and published her first paper on making monoclonal antibodies specific for cholera toxin. The lab was at Harvard University and had researchers at all different levels – MDs, postdocs, masters, bachelors degree – providing many educational opportunities for her. She was inspired by the work and seeing the MDs come back with pictures from their trips to India and with clinical isolates of cholera for research. So, after having graduated from college without knowing what she wanted to do, just two years later, she knew that she wanted a PhD.

The Implications of Basic Research

After earning her PhD from UCLA, Whoriskey contacted Dr. Jack Szostak, a professor at Harvard, to seek a post-doctoral position in his lab as she was interested in his work. Szostak was researching how the DNA sequences at the tips of chromosomes, known as telemeres, are properly replicated. This is a fundamental mechanism in the cell. It turns out that this basic research ended up showing that telemeres are highly predictive of aging and cancer, and there is now an entire field of research studying this. From this endeavor, Whoriskey saw first hand how basic research has the potential to make a huge impact on human health. In fact, Szostak won a Nobel Prize in Physiology or Medicine for this work in 2009. After this breakthrough, more people entered the field and began conducting additional research that stood on Szostak’s shoulders. This shows how science is advanced over time through the successive efforts of many. As Whoriskey puts it, “Many more researchers come after us and build on our accomplishments.”

The Ability to Switch Careers

Even though it is not unheard of, there is a strong sense that someone is committing career suicide if he/she chooses to switch careers or fields too late in life, and this sentiment can often leave someone feeling trapped. Whoriskey, however, was freed from that restriction on her career. Shortly after she arrived at the Szostak lab, he shifted the focus of his research to studying the role of self-replicating genetic polymers and the transition from chemical evolution to biological evolution, and she began working on that project. Now, he has emerged as a leader in this field as well. According to Whoriskey, “It takes a certain attitude to start in a new field even though there might be pressure not to. A lot of people, especially students, feel pigeon holed. There are certainly barriers to entry, but it is possible to change fields if you are properly motivated and if you have the drive, interest, and support to switch fields.“

Serious Scientists & Academia

After finishing her postdoc, Whoriskey felt a lot of pressure to go into academia. At that time, as she puts it, “Serious scientists did not go into the private sector.” However, she was more interested in applying science to drug development. Although she did not feel that being a professor aligned with her goals, she believed that people would be disappointed in her if she went into the private sector. She had to get comfortable with the idea of disappointing others and choosing the path that was right for her. Further, as Whoriskey explains, “There are norms out there that we often feel we can’t go against. These are norms not rules. You don’t have to go with the crowd. Your own inner voice is a powerful voice. Respect it.”

The Daptomycin Story

Antibiotic Resistance

whoriskey was aware of and concerned about the significant issue of antibiotic resistance. this graphic shows how quickly antibiotic resistance bacteria is identified following discovery of new antibiotics. (source: http://s.telegraph.co.uk/graphics/projects/antibiotic-resistance/) whoriskey was aware of and concerned about the significant issue of antibiotic resistance. this graphic shows how quickly antibiotic resistance bacteria is identified following discovery of new antibiotics. (source: http://s.telegraph.co.uk/graphics/projects/antibiotic-resistance/)

In the early 1990s, Whoriskey met with a chemistry professor and a biology professor at MIT. They were forming a company to test some small molecules developed by the chemist against assays developed by the biologist to look for antibacterial activity. This company would become Cubist Pharmaceuticals. As Whoriskey explains, they had to overcome some really big barriers to entry as a company. At the time, all of the big drug companies were moving away from antibiotic development programs to work on more lucrative drug development opportunities. Yet, the problem of increased hospital-acquired drug-resistant infections was already emerging and the trend was going in the wrong direction. Infectious disease was on the rise, and new antibiotics would be needed to treat it. Within two years of starting the company, a number of companies thought about getting back into antibiotic development due to the increase in drug-resistant pathogens.

ACCORDING TO THE REVIEW ON ANTIMICROBIAL RESISTANCE CHAIRED BY JIM O'NEILL, IF NO ACTION IS TAKEN BETWEEN NOW AND 2050, THIS CRISIS WILL COST $100 TRILLION AND LEAD TO 300 MILLION PREMATURE DEATHS. (SOURCE: REVIEW ON ANTIMICROBIAL RESISTANCE 2014) ACCORDING TO THE REVIEW ON ANTIMICROBIAL RESISTANCE CHAIRED BY JIM O’NEILL, IF NO ACTION IS TAKEN BETWEEN NOW AND 2050, THIS CRISIS WILL COST $100 TRILLION AND LEAD TO 300 MILLION PREMATURE DEATHS. (SOURCE: REVIEW ON ANTIMICROBIAL RESISTANCE 2014)

Listening to the Science

Although Whoriskey’s team was working with good small molecule inhibitors of enzymes in vitro, they were never able to identify a molecule that could pass the outer membrane of the bacterial cells in order to kill the cell. The science worked in that it gave them data they could base decisions upon, but the data was telling her team something important. They needed a molecule that could pass through the bacterial membrane. They decided to listen to the science, stop what they were doing, and try something else.

In the hunt for a molecule that could pass through the bacterial membrane, Whoriskey and a team of Cubist experts talked to companies that had stopped antibiotic research to see if there was anything they had stopped working on worthy of further development. That was pivotal.

mount ararat in turkey – the source of the daptomycin soil sample (Source: Wikimedia commons, the free media repository, www.andrewsevag.com) mount ararat in turkey – the source of the daptomycin soil sample (Source: Wikimedia commons, the free media repository, www.andrewsevag.com)

Eli Lilly had run a program where employees brought back soil samples from their vacations, which was legal at the time. (Now, it is necessary to follow rules and regulations protecting plant, animal, and human health and potential soil ownership rights.) Eli Lilly had conducted assays to see what natural product extracts and molecules kill whole cells and had a molecule that fit Cubist’s criteria. The team identified daptomycin, which came from a soil sample from Mount Ararat in Turkey.

Out-of-the-Box Business Strategies

(source: Asm clinical microbiology reviews) (source: Asm clinical microbiology reviews)

In preclinical studies, Eli Lilly thought that it had seen some muscle toxicity that would prevent additional development and was focused on other projects at the time, so the molecule was shelved. Whoriskey managed a due diligence team that evaluated the Eli Lilly data. They decided to evaluate whether they could achieve a dosing regimen that killed the pathogen but did not cause the same toxicity and signed an agreement with Eli Lilly to pay a royalty on drug sales. This was a paradigm-shifting business strategy at the time as Cubist, a small biotech, successfully licensed IP from Big Pharma versus the other way around. According to Whoriskey, “Chance here truly favored the prepared mind. Cubist experts knew what they needed, and they went for it.”

The drug turned out to be extremely successful and is capable of treating multi-drug resistant Staph aureus bacterial infections (MRSA). Cubicin was one of the first new chemical classes of antibiotics to be approved by the FDA in over 50 years. The drug has been used to treat more than one million patients, and Merck purchased the company for $9.5B in 2014.

The Profit Motive & Curbing Antibiotic Resistance

Under current market dynamics, pharmaceutical companies wish to sell as much product as possible to rake in as much profit as possible. However, excessive antibiotic usage, including unnecessary prescriptions and usage of antibiotics in animal feed to speed up growth or prophylactically, accelerates the emergence and prevalence of antibiotic-resistant pathogens. With this is mind, antibiotics should be treated as precious resources and preserved for cases when they are necessary. It is challenging to square the motives of a for-profit company with the need to treat antibiotics as precious resources.

For Cubicin, Whoriskey’s team focused its market on the proper use of the antibiotic to treat sick patients for indications approved by the FDA and it succeeded. According to Whoriskey, “To me it’s simple: Number 1: Do the right thing. Number 2: It will always be possible to do well by doing good. You don’t have to over prescribe drugs or gauge drug prices to receive profit necessary to remain a sustainable business. I believe that making drugs that people need is a sufficient and viable business strategy.”

Business Edge – Understanding the Science

Throughout her career, Whoriskey has worked not only in academia and on the science side but also on the business side. She has led scientific and financial due diligence teams and collaborations in the drug development process and managed intellectual property estates and patent litigations, including cases that have reached the Supreme Court. To be good in a biotech business deal, Whoriskey finds that, “You really have to understand the science. In this sector, understanding the scientific objectives when you are working on the business side gives you an edge and helps you look at something in a new and different way.”

Whoriskey possesses that true entrepreneurial spirit. Instead of identifying barriers and saying stop, she is always looking at how to get around them. This ability to think differently and align with supporters has allowed her to successfully navigate obstacles that have stopped others.

Other Successful Ventures – Momenta & Moderna

Following Cubist, Whoriskey became a member of the founding Executive Teams of two additional top successful biotech companies in Massachusetts – Momenta and Moderna – and she is now working on a fourth one – PNA Innovations.

Whoriskey led Corporate Development for Momenta Pharmaceuticals with the goal of expanding access to high quality, more affordable medicines. At the time, there was no regulatory process at the FDA in place to approve a generic version of highly priced recombinant protein drugs or complex mixture drugs made from biological source material. There were only the following routes available: NDA (new drug application), ANDA (amended NDA), and BLA (biological license application), and a 1984 generic drug regulation only applied to single small molecule treatments. Yet, there was a need in the marketplace for generic versions of drugs derived from biological sources, and Momenta had the technology to prove to the FDA that they could make products that were chemically identical to the brand product. By showing chemical identity, the possibility existed that they could skip clinical trials and therefore bring the generic drug to market at a lower development cost and also price the drug lower than the brand.

Thanks to foresight and some out-of-the-box thinking, Momenta essentially pioneered the field of biogenerics and achieved the first FDA approval for a complex mixture generic drug, Enoxaparin, to prevent and treat deep vein thrombosis and acute coronary symptoms. It was the most successful generic drug launch ever in the US and saved the US healthcare system hundreds of millions of dollars. Momenta also received FDA approval for Glatopa, a complex generic version of Copaxone (complex mix of peptides), the leading product to treat multiple sclerosis. Now, the company employs more than 300 people and is valued at more than $1B.

Subsequently, Whoriskey was senior vice president of technology strategy on the Founding Executive Team of Moderna. Moderna is pioneering messenger RNA (mRNA) therapeutics, a novel technology to develop therapies faster and at lower cost to treat a variety of diseases, including cancer and infectious disease. She helped develop a science and business strategy that raised $450M in investment funding, the largest biotech venture financing on record. Currently, Moderna employs more than 300 people.

Onto her latest adventure, Whoriskey is now back working on her fourth biotech venture, PNA Innovations (PNAi). The company has pioneered the invention of novel peptide nucleic acids with potential uses in diagnostics and therapeutics. She is working with the team to apply the technology to human health.

Combining her scientific mindset with her entrepreneurial spirit, Whoriskey has worked on every aspect of the drug discovery process starting with the big science idea and seed venture capital to scientific proof of concept and initial public offering all the way through to follow-on financings and FDA drug approvals.

Women in Science

whoriskey (second from right) with small world initiative high school researchers from the hockaday school at swi's 3rd annual symposium at asm microbe in boston. whoriskey (second from right) with small world initiative high school researchers from the hockaday school at swi’s 3rd annual symposium at asm microbe in boston.

While often the only woman on the executive team, Whoriskey has been fortunate to work in very ethnically diverse environments with men who were supportive of her career and her contributions. Interestingly enough, Whoriskey notes that Szostak has observed that most of his postdoc inquiries are from men, and she wonders if she would have had the guts to write him and request a position as she had done if he had already won the Nobel Prize. She suspects that may have intimidated her and held her back, unnecessarily so. Recognizing the challenges many women face, Whoriskey advises women, “I believe I can always be kind, but in making tough decisions, I can’t always be nice and please everyone. So stop worrying about wanting everyone to like you, and focus on doing the right thing. It’s liberating.”

She also hopes more males step up to be involved in the conversation of equal treatment of women and share proper behaviors. She has worked with so many capable women in her career that she sees no credible reason why there are not more women in executive roles. She is hopeful that discussions about this are ongoing in society and that in her lifetime she will see these trends reverse.

The Future of Antibiotic Discovery

whoriskey (second from left) with small world initiative student researchers from the university of pittsburgh at swi's 3rd annual symposium at asm microbe in boston. whoriskey (second from left) with small world initiative student researchers from the university of pittsburgh at swi’s 3rd annual symposium at asm microbe in boston.

Whoriskey contends that, “Antibiotic resistance should be seen as a public health priority. It is a problem with the potential to cause significant human harm to men, women, and children alike, and it is not going way. All available resources should be brought to bear on the problem. This includes immediately implementing policies to further incentivize research in this area. Groups like the Small World Initiative are invaluable in educating, incentivizing, and inspiring great students to go into the field just as I was encouraged to do when I was in college.

Whoriskey adds, “No one has a monopoly on who will discover the next antibiotic, and furthermore, the more bright minds involved, the better outcome for humanity. Drug discovery is an amazing thing to do with your life. It takes curiosity, passion, training, persistence, persistence, and persistence!”