We were joined by Sarah Dykstra, who worked in the early drug discovery group at Amgen. Many of our postdocs and PhD students will end up in R&D, so its a great opportunity to learn about your potential future career.
Big thank you to Thermo Fisher Scientific for sponsoring this seminar! Remember that if you need any support from Thermo Fisher, feel free to reach out to our friendly Account Manager, Adam Semple!
Here are some insights from the seminar on the drug discovery pipeline:
(A copy of the slides can be found at the end of the post!).
Sarah got her Bachelor of Science from Stony Brook University and then went on to be a research associate in Amgen’s Cambridge Hematology Oncology Group… and then got bored and got her PhD from Brandeis University.
More on the industry job…
- She performed screens of small molecules and investigated candidates for potential therapeutic intervention.
- Identified targets from the literature and validated that the data was reproducible (as much of the published data is not!).
So, how do you make a drug?
First, you need to determine what you are screening for and what your downstream reporter might be.
Steps in Drug Discovery:
- Discovery Research
- Preclinical Research
- Clinical Research
- Regulatory & Manufacturing
- Launch – sale of product.
Only about 1 in 5,000 molecules make it through discovery to launch and this entire process takes over a decade!
What do you do in discovery research?
You think about what candidate genes would be amendable to therapeutic intervention by reading the literature and attending conferences and meetings.
You need to find a good target, one that has minimal side effects.
The other major function is to design cell based assays to validate therapeutic targets, then screen small molecules to determine several initial “hit” compounds.
(A hit is something that is potent at a micromolar range whereas a lead is a modified hit that has potency at the nanomolar range, this is important to minimize off target effects).
How do you decide what target to work on?
It is generally a joint decision based on the team and the literature.
Goals of discovery research:
- Identify a candidate to interrogate
- Design a screen (and counter screen)
- Find a series of hit compounds:
- Refine specificity and potency via modification of chemical structures (to find a number of leads)
- Determine a lead compound to bring through to pre-clinical development.
Difference between pharma and biotech:
Pharma compounds used to be “chemical” compounds and had libraries of tens of thousands of compounds in libraries, whereas biotech companies are from the era of recombinant DNA and used biologics (protein based therapeutics). Now, both compounds could have millions of compounds that they routinely screen.
How your drug works in vivo!
Determining the optimal in vivo dosing, safety profile, PharmoKinetics (the life span of the drug), PharmoDynamics (how the body metabolizes the drug and how bio-available it is) and ADME (absorption, distribution, metabolism and excretion of the drug – much of this influences the side effects).
Design stable API formulations and good manufacturing practices (GMP) to develop analytical methods
… for incorporation into an IND filing.
Goals for preclinical research:
- Determine ADME, PK, PD, toxicity
- Finalize a lead compound and scale up manufacturing
- Determine a dosing schedule for first-in-human trials
- Develop a clinical plan and preparing a new drug product
- Prepare for IND filing
Question: How many animals are required?
A: Several hundred and it generally starts with rodents and rabbits and ends with higher mammals such as dogs and pigs. Monkeys are being phased out for a number of reasons.
– Designed to determine safety and dosage in humans, efficacy and side effects in increasingly large human populations. This is required to account for polymorphisms and other genetic modifiers than can influence drug bio availability and metabolism.
– A clinical trial is based on data obtained from pre-clinical research on dosage, PK/PD and toxicity which requires FDA approval of your NDA.
Phase 1: 20 – 100 healthy volunteers to evaluate safety and dosing.
Phase 2: More patients to assess drug effectiveness and further evaluate safety.
Phase 3: Largest number of patients involved, further studies on safety and efficacy in larger populations.
Goals of clinical research:
- Obtain safety, efficacy, dosage and adverse effect data
- Use this data to convince the FDA that there is evidence from preclinical and clinical research that a drug is safe and effective for its intended use (NDA filing).
- Finalize lead compound and manufacturing.
How many drugs are pulled off the market after Ph4 trials?
In the case of cancer drugs, these are rarely pulled due to the terminal status of the patient.
The riskiest step is within the discovery and preclinical steps whereas the typical failure point is around phase 2 – during clinical trials.
Making a drug is RISKY business, costing $1-2 billion dollars and close to a decade (if not more) with a low success rate.
Rational drug design is a big, relatively new area in which you design the drug to fit the site, rather then screen drugs that might incidentally fit your target.
What Sarah learnt from working about industry:
- Team work and soft skills are highly sought after (and required!)
- You won’t be abandoning science, but you do need to accept that priorities change rapidly.
- Success is carefully defined and those who exceed expectations will be advanced and well rewarded.
- Not all companies are run similarly, expect cultural and management differences, a start up does not run like a large company.
- Industry positions are highly competitive, expect to work with the best
- You will constantly have to learn, network and delivery to succeed.
- The most successful industry scientists have excellent time management and communication skills and are highly productive.
This is talk is part of a series! The next seminar is a case study on science and strategy behind the development of two commercial drugs: epoetin alfa (Epogen), a biologic from Amgen and Gleevec (Imatinib), a small molecule from Novartis.
Click here to download the slides from the talk! – Drug Design Talk_1 Sarah (pdf).
We were joined by world renown and innovative Tufts Chemistry Professor and HHMI investigator David R. Walt, PhD on "how to develop your next big scientific idea" for success in Academia and Industry.
Here are a few highlights from the talk:
David Walt’s thoughts
On being in academia:
You really need to determine your motivation: What are your goals?
Everyone assigns different weights to different things based on their own personal situation.
This will help you determine where you should be …
Ask the following question for any new idea or project:
If it works and gave you the best possible result, would that make a difference to anyone other then you and your research advisor?
If it doesn’t – then it’s probably not a really good idea.
How do you come up with a new idea?
Start with the literature…
1. Read very broadly. Don’t start with your niche area. Get an idea of what the landscape looks like, the big picture. What is happening in science and what are the problems that people are working on?
2. Can you think of a different perspective, coming from a different area? example, as a chemist, looking at an immunology question.
3. You don’t need to have a particular focus or agenda in your reading. Look at thebigger landscape of problems for perspective.
Reading very detailed can cause you to think everything is covered, you get lost in the weeds… one solution:
Stare into space.
Give your mind a break. It is easy to get overwhelmed be all the information.
Observe people in action
– Watch the experts
– You may see issues or problems that you can undertake as your idea.
It’s dangerous to get research ideas from your experimental results that deviate from the norm as they can lead you astray. You can get moved so far off track that you never find your way back to the main path.
How to decide if you should change your path?
You need to do risk analysis. Are the paths very different? Do you have the resources and materials to do it easily?
You know when you have a good idea – it’s almost a spiritual experience.
How do you trust your intuition?
Be an optimist! Pessimists don’t get very far in research as things will fail if you expect them to.
If a grant or paper was rejected you need to probe why it was rejected. There's usually some valuable information there.
What one piece advise would you give yourself from grad school?
- Be opportunistic, take the long term view, you need to get funding and you need to be published. Don’t start with trying to cure cancer.
- Pick problems that make a difference.
On the benefits of being resource limited:
If you are NOT resource limited, sometimes you do stupid things because you don’t have to be careful. Resource limitations force you to work intellectually.
When do you share your idea with your PI?
When you come up with a really good idea – just zip your lips! Do not spew it out. Think about it.
The Professor is In: Karen Kelsky, PhD, continued to explain how to hack the academic job search and focused on the art of acing the interview.
The Foundations of Interviewing
- time management
- anticipate the timing and number of questions
- in a conference interview, anticipate 5 questions and 3-4 minute responses
- practice them ahead of time!
- use bullet points
- image management
- lose your graduate student mentality
- own your expertise!
- imposter syndrome
- confront it
- women suffer from it the most
- everyone experiences it
- you were picked for an interview- you are good enough
- the question is how effectively can you prepare to clearly articulate your research?
How to prepare:
- Learn the names of the interviews and research their work
- Check course listing
- Make a cheat sheet of the department
- Deliver what the department needs, not what your dream research is
Describe your dissertation and postdoc:
- Prepare to be clear and concise
- You should be able to describe each in five sentences
Describe your tenure publication goals:
- Be brief
- Address how you would deal with a diverse range of students
- How would you incorporate diversity in your teaching materials
- Delve into your personal background
- How can you administratively support diversity
- Demonstrate awareness of inequities and challenges of underrepresented minorities and the negative consequences of this
- How can you personally and administratively address this
- Avoid being a supplicant
- Start from a position of psychic parity
- “look at how well we match”
- this department’s interests and my own match so well
- I can contribute to the interests of Dr. X and Y by doing courses on QQ
- “look at how well we match”
“Questions for us”:
- Be sure to know your environment
- At an R1, ask about research
- At a teaching college, ask about teaching
- be concise and prepare your thoughts ahead of time!
- lack of focus
- inappropriate speech patterns
- don’t use hedging language
- I think, I hope, I want (hesitation)
- It seems like (insecurity)
- I really love, I’m passionate (hyper-emotionalism)
- I’m sorry (lack of authority)
- Uptalk (lack of authority)
- don’t use hedging language
- Being caught unprepared
- elevator speech synopsis of your dissertation
- be able to explain your contribution to your field
- how do you mentor undergrads and grads
- handling diversity
- teaching philosophy
- Odd body language
- Your interview is a performance
- Make a visual impression the moment you enter the room
- control your visual impression:
- your eyes, hands, shoulders
Today we are joined by Paula Chambers, founder of Versatile PhD for a seminar by the Sackler GSC. Paula runs a successful online repository of forums and career information for PhDs.
- Versatile PhD was started as a listserv for career options for non-Academics in the social sciences.
- Based on Institutional subscriptions: 75 universities and 63,000+ members
- Supportive discussion forms
- Contain ACTUAL PhDs who contribute to discussion forums about specific career topics. Have diversity of panelists. Panelists introduce themselves on Monday and take questions from members during the week.
- Rich source of PhD-specific information
- Job board: volunteer posted from Versatile PhD members, non exhaustive and PhD requiring, but it is PhD appropriate
- Local meet-ups! Sarah is our local rep who hosts regular meet ups in Boston!
- PhD Career finder: A list of careers available to different spheres of PhDs (humanities and STEM). Each job contains descriptions for that job, starting points, advancement, disciplines, personality and outlook and how to get started.
- The Boston Versatile PhD group has a LinkedIn group (which you can join!) and does contain recruiters and hiring managers (so go ahead and join!).
- Hiring success stories of people that transitioned into other careers. Actual resumes, cover letters & application materials from real people!
- Summaries of the discussions from panelists from the forum.
- Career autobiographies: Stories from PhDs about their career journeys.
- The Power search: Allows you to search versatile PhD database for multiple criteria at once, including discipline, area and job. Allows you to connect with members who are in the job that you want. Some members can’t be contacted on LinkedIn on a basic account, whereas you can do so on Versatile PhD.
Core message of Versatile PhD: You are versatile! You can do many things! Non-Academic careers are okay!!
Versatile PhD in Greater Boston from Sarah Dykstra
Co-led with Sarah and Nikki Boots (both PhDs).
Main focus of Boston Versatile PhD:
- Networking, mentoring and support, especially for social scientists.
- Twice a month social events (usually around Cambridge).
- Monthly Thursday evening pub night
- Sunday afternoon lunch
- Meet recruiters, PhDs employed in industry, grad students, postdocs & job seekers.
- Workshops & training: bring people in from around the world via teleconferencingRecent examples:
- Resume writing
- Informational interviews
- Identifying translation-able skills
- How to market yourself to employeers
- Managing stress & Imposter syndrome
- Talking to your advisor
- LinkedIn profile
- Social stuff and fun
- Pub networking night
- PhDs in the park
- A night in Legoland
- About 150 active people and over 700 subscribers in Boston
- Highly motivated members!
Connect with the Versatile PhD here:
We were lucky enough to be joined by Cliff Ramsdell, PhD, Product Development Manager for Flow Cytometry in North America for Thermo Fisher Scientific. Cliff spoke about careers in commercial sciences as a often overlooked but richly rewarding way to use your analytical and research skills!
Here are some highlights from the seminar:
- Incorrect misnomer that leaving academic science leads to job dissatisfaction. This is not the case!!
- Job descriptions are the “ideal” candidate and often do not represent the person that ultimately gets hired. Apply for jobs even if you don’t hit all the requirements! You don’t necessarily know the minimums until you apply for a job.
- Networking ultimately nets you the job: its the networking you do NOW that can help you land your future position. Cliffs’ first job outside of industry was through a friend from graduate school who had changed jobs.
- Sales provide scientists with solutions to their problems.
- Product Managers: liaise with scientists and create new products from the suggestions from the scientific community
- Market development manager: help connect researchers with what they may need to make their experiments more efficient.
Things to consider:
- Get really competent in one application area, and this can help you with conversations on the business side.
- Build your network!
- Get out of the lab, build relationships and friendships!
- Have colleagues in other departments (help with your research and your career!)
- Participate in activities, inside and outside work!
- Talk to sales reps and industry contacts.
- Collaborate and communicate with researchers outside of your field!
- Attend conferences and external courses (sometimes you want to invest in yourself).
- Work on your communication skills (both written and verbal)
- Know your strengths and weaknesses
- Leverage your strengths
- Work on your weak areas
- Have some direction – get insight on what you may be interested in.
- Honest self awareness – what do you really value? What do you really want?
- Develop options – don’t get pigeon-holed, try to expand your options no matter what you do.
Initial job opportunities outside academia:
- Field Application Specialist
- Hybrid position of a narrow focus area.
- Do a lot of demos, product education.
- They are knowledgeable in all facets of the technical information.
- Scientific talks on applications.
- They don’t really sell, although they collaborate closely with sales managers.
- Tend to travel a lot depends on the territory (although Boston is relatively dense).
- Different flavors: Product development (develop new products), application scientist (generate experimental data to back up products) and often communicate to scientists.
- Tech Support
- If you are not as comfortable with face to face contact but great training
- Can be good hours
- Less structured but very flexible
- Have goals and benchmarks to hit quarterly
- Application Specialist
- “Super” FAS.
- Very skilled scientists as resources to solve problems
with additional certification:
- Patent law/technology transfer – need scientists who understand the science to be able to patent the process.
What you should consider when you are looking for a new job:
- Is it a challenge? Doesn’t want to be too easy or too difficult
- Balanced life style (different for everyone!)
- Sense of purpose. Leaving the bench DOES NOT mean that you are leaving this behind!!
- Knowing the options
What is marketing?
It’s unlikely to leave academia and go straight in, but it is achievable in 3-5 years
- Advertising is only part of it.
- A marketing professional stimulates demand for supply in the market place and engages all parties involved.
- Marketing is used to identify the customer, to satisfy the customer and keep the customer.
- It’s about understanding the business!
- How the company brands themselves, what they focus on.
- Great book to read about marketing: Made to stick by Chip Heath and Dan Heath
- Marketing in life sciences:
- No matter what: Need to be passionate about what you do!
Why a PhD?
Marketing is about understanding a complex problem. You need:
- market research
- psychology, behavioural studies
- communication skills
Most important aspects of a PhD:
- teach yourself to learn
- scientific process
- communication skills
- challenge of the unknown: test, fail and redirect
How to get in:
What are the 3 most important skills needed to excel in the field:
- Communication, subject matter knowledge and humility
What is the general career trajectory:
Generally you start as sales or field application specialists (salary is ~ 6 figures) and can move up to other careers
Is being an international academic (J-1), a crux in entering this field?
Mostly yes. Getting sponsorship is costly and expensive
How applicable would these opportunities be to an MD?
Depends on training and career goals
And remember: You are AWESOME! You are in an amazing place with amazing research going on. DEVOUR everything! All of the science, watch on a broad scale everything that is going on in Boston and continue to be engaged. What differentiates you from other people, perhaps more experienced is that you are hungry! Every time you go into an interview, portray that! Go GET YOUR MONEY! You are worth a lot of money!
(direct quote from Adam, Account Manager for Thermo Fisher!).
Here are some tips from Dan:
- What is your Mission: Decide what your immediate and longterm goals are when networking. Where do you want to be in 10 years?
- Next, make yourself unique and easily distinguishable from others in your field. Using these ideas, develop an elevator pitch. Be interesting, but succinct.
- To establish your network, find mentors and mentor others. This will form the beginning of your future network.
- Once you’ve begun to establish your network, make deeper connections. Learn to market yourself and your value.
Developing your mission:
- What is your deep passion? People are attracted to true passion.
- Be specific and leverage your gifts to make yourself stand out and be unique. Bridge disciplines.
- Work on something important (not incremental). Don’t be afraid to embrace failure.
- Use the “three strikes” rule. Keep trying, and if it doesn’t work out, move on.
- When you succeed, dive in and become the expert.
Cultivate mentors and mentor others
- Ask for help and give help freely to others
- Use these mentoring relationships to form the basis of your network
- Be openly appreciative
- This should be short -less than 1 minute
- Demonstrate the relevance of your work and your passion
- Be compelling and memorable, and meet the needs/help the listener. What can you do for your listener?
- Have a “small business” mentality. You have a product – your ideas – to sell.
- Be creative in your marketing. How can you as a unique individual best get your message across?
- Use the opportunity to be memorable to get your message across at meetings. Leverage the opportunity.
- Be open to opportunities and seek them out.
- Do more for your connections than they do for you.
- Use social networking- LinkedIn, Twitter, Facebook, Quora.
The Point of an Academic Conference
- How to make connections
- Demonstrate mastery of your subject area.
- Be a leader (rather than a follower). Do you recognize an opportunity or unmet need that you can address?
- Eat with others – it’s an easy way to socialize!
- Build your persona. Introverts can learn to build their “extroverted” networking personality.
- Be memorable. Approach people with the idea of who you want to build connections with.
- Follow up to cement the relationship (e-mail, etc.).
- How to prepare for a meeting
- Develop a professional, but authentic persona.
- Prepare ahead of time. Is there someone you’d like to collaborate with? Postdoc with? Check out the attendees- consider emailing them ahead of time to schedule a cup of coffee.
- Be brave and meet new people. Most people welcome such opportunities and want to meet you.
- How to work during a meeting
- Don’t spend time with your friends.
- Use meals, mixers and social events strategically.
- Ask about their work. Do you have an idea about how to collaborate or help their research.
- Ask about follow up steps – exchange business cards and note down what you talked about.
- Ask questions at sessions and follow up (see step 1.6!). If you’d like to establish a relationship with someone senior, follow up asking them to be a mentor. Would they be willing to meet for coffee occasionally.
- Define your goal.
- Develop your unique skill set to meet this goal
- Build your network
- Market yourself
- Enjoy the journey!