Interview with leading HIV vaccine researcher – Prof. Sir Andrew McMichael

Introduction

Continuing our investigation into medical research careers, we interviewed Prof. Andrew McMichael. Andrew is Director of the Weatherall Institute of Molecular Medicine in Oxford, and focuses especially on two areas of special interest to us: HIV and flu vaccines.

Our aim in this interview was to gain the perspective of someone who had entered medical research as a medic, whereas our previous interviewee, John Todd, entered as a biologist, and to gain the perspective of a senior researcher focused on infectious diseases rather than genetics. We also wanted to test some hypotheses from our two previous interviews (here and here).

Andrew was introduced to us by John Todd. The interview was conducted in person and recorded. The following is an abbreviated selection of key quotes, reorganised for clarity.

Key points made

• Andrew would recommend starting in medicine for the increased security, better earnings, broader perspective and greater set of opportunities at the end. The main cost is that it takes about 5 years longer.
• In the medicine career track, you qualify as a doctor in 5-6 years, then you work as a junior doctor for 3-5 years, while starting a PhD. During this time, you start to move towards a promising speciality, where you build your career.
• In the biology career track, get a good undergraduate degree, then do a PhD. It’s very important to join a top lab and publish early in your career. Then you can start to move towards an interesting area.
• After you finish your PhD is a good time to reassess. It’s a competitive career, and if you’re not headed towards the top, be prepared to do something else. Public health is a common backup option, which can make a significant contribution. If you’ve studied medicine, you can do that. People sometimes get stranded mid-career, and that can be tough.
• An outstanding post-doc applicant has a great reference from their PhD supervisor, is good at statistics/maths/programming, and has published in a top journal.
• If you qualify in medicine in the UK, you can earn as much as ordinary doctors while doing your research, though you’ll miss out on private practice. In the US, you’ll earn less.
• Some exciting areas right now include stem cell research, neuroscience, psychiatry and the HIV vaccine.
• To increase your impact, work on good quality basic science, but keep an eye out for applications.
• Programming, mathematics and statistics are all valuable skills. Other skills shortages develop from the introduction of new technologies.
• Good researchers can normally get funded, and Andrew would probably prefer a good researcher to a half million pound grant, though he wasn’t sure.
• He doesn’t think that bad methodology or publication bias is a significant problem in basic science, though it might be in clinical trials.

Some updates for us

• All of our interviewees have agreed that good researchers can generally get funded, which also fits to what we read in GiveWell’s interviews, so we’re inclined to accept this.
• John Todd strongly preferred additional good researchers to money, while Andrew was less sure, so we slightly updated in favor of money being important.
• We’re still unsure about the medicine vs. biology track, though are leaning towards medicine for most people due to the stronger back-up options and higher earnings.
• Both Andrew and John agreed that quantitative skills were valuable, so we’re inclined to accept this.

The interview

Background

Andrew comes from a family of medical researchers. Always knowing he wanted to do research, he studied medicine, then did part 3 biochemistry at Cambridge, 3 years of clinical practice, and a PhD. After his PhD he went to Stanford where where he worked as a researcher in Hugh McDevitt’s lab, before moving to Oxford in 1977. Today, he primarily works on flu and HIV vaccines.

Did you ever consider doing anything else?

“I always wanted to do research that was related to clinical medicine, and in immunology you can either go into infectious disease or autoimmune disease if you have a clinical interest. While I was at Stanford I did some work on rheumatology. About that time I got interested in the HLA system, then how it might translate into immune responses…work on the T-cell recognition of viruses came out. I thought, ‘that’s a really good thing to look at – look at virus infection’ So I started working on flu, which I’m still working on. I’m going to China about flu today. And then along the line HIV came along, so then I worked on HIV. I always felt these were clinically important topics.”

Getting started in this career

“If you’re going the PhD route, you want to go to the best labs in your general area – neuroscience, immunology, cancer, cell biology. You just need to go where the best science is – the most Nature papers, the most Cell papers.

“If you’re going the clinical medicine route, you may see an opportunity like dermatology, where there’s no many people going but you see great opportunities. Dermatology is fantastic for clinical research, because you can access the tissue. There’s a whole host of diseases that are not well understood, relating to major systemic diseases, like skin rashes in HIV, or in autoimmune diseases.

In medicine, you’d qualify in medicine, then do about 3 years of training, and maybe a bit more, and start heading towards a speciality (like cardiology, infectious disease, dermatology). You just start seeing what kind of research is going on in that field, who the best people are and where you might go. You’re doing junior doctor jobs, and trying to decide which direction your career is going. Then you might pick an area. Then you start developing a career.

“It’s very important to have mentors, people who advise you. They’re your teachers initially, then your friends and advisors.”

Is it better to start by doing an MD?

“You need to put aside close to 10 years: 5-6 years for medical degree and junior training which is 3 years. You’ll also need to carry on doing some medicine while doing your PhD. Overall it takes 10-12 years before you’re fully qualified in medicine and able to run a research program. It’s tough, especially if you want to start a family.”

What would you recommend to someone who’s starting their career?

“If it was my son or daughter, I’d say do medicine. There’s more security, you’ve always got a second career as a fall back. There are a lot of different opportunities in medicine that you can explore. When you’re 21, you may not see the best things to work on.

“One advantage of medicine is that you have a bit of extra time to spot an opportunity. That might help you find something that’s unexplored, but turns out to be important. One example is that there’s some fantastic things going on in Ophthalmology: gene therapy and stem cell work in the eye. Coming from a PhD background you might not see that being a place to go.

“More generally, if you want to see patients, you have to do medicine. It’s a longer process. but there’s more opportunities at the end. There’s better salaries. If you want to get to research fast, go the PhD route. It’s tougher, and there’s more competition and it’s a sharper pyramid – though they tend to be the ones who win the Nobel Prizes.”

To what extent does going into research as a medic hamper your earnings?

“In the UK it’s not too bad. Most of the research will be in medical schools, and as a clinical researcher you’ll be on a very similar salary to other medics. Where you’ll lose out is in private practice. Some medics do 1-2 days a week and almost double their earnings! It’s much more of a problem in the US.”

Increasing your impact within the field

What are some of the promising areas right now?

“Stem cell research is amazing and exciting. I think neuroscience is. The brain is incredibly complex, but you’re beginning to be able to get insight into how it works. Physiciatry is probably ripe for development and explanation of psychiatric disorders, using combinations of genetics, cell biology and neuroscience. In my own area, the HIV vaccine problem is a big, big question that is now open to quite sophisticated science to underpin it and develop it. I think there are many more, but those are examples. They’re exciting to me, but talk to different people and you’ll get different views.”

What are the main things preventing researchers from producing more value? For instance, Iain Chalmers has argued that 90% of medical research is wasted due to bad study design and other biases.

“I think these kinds of issues are more of a problem in clinical trials. You’re not going to get funding to do a laboratory based project if it has been done before or it isn’t a very sound idea. The process is very rigorous.”

“I agree that negative results tend not to be published, which does bias the field occasionally. And sometimes something gets published, but there’s never any follow up, so you might doubt it’s a real result. But in basic science, the word normally gets out one way or another. It’ll probably be mentioned in reviews eventually.”

We asked Andrew about how feasible it is to target your career at neglected areas. As explained above, in the PhD route, he stressed the importance of starting in the best labs
In the clinical route, you could look to pick a promising speciality in the 4 years after qualifying.

What strategies could you use for having more impact? For instance, our previous interviewee recommended trying to secure long-term funding to work on a difficult problem and avoid bandwagons.

“That’s for a bit later. I think it’s difficult. Many people were not thinking about clinical application when they made discoveries with huge impact on clinical medicine.

If aiming directly at impact isn’t what seems to work, what do you focus on instead?

“Focus on what’s good basic biomedical science. Stem cell therapy is probably going to have a huge impact on medicine, but it stems from a very basic level. The people who started that work from the very beginning, were not thinking about treating patients. I think a good strategy is work on basic science, but keep an eye out for applications that might arise. More people are doing that now.

Evaluating ability

What kind of CV would make your face light up?

“I’d look for a good first degree – first or a 2.1, though there are various means to get through with a 2.2 (note: a first or 2.1 is equivalent to a GPA of 3.2-4). You’d look at where they went. It’s quite a good indicator of academic excellence. Then I’d l look at what they did in their PhD. Did they publish any papers? Bear in mind they can get put on a project that’s not top notch, and it’s not always their fault.”

“Then you’d look at what their supervisor said about them, or their head of department. A lot of people look quite similar up to this point. They generally have firsts or 2.1s from Oxford, Cambridge, Imperial, Edinburgh or so on. They’ve done a PhD and got 2-3 publications. They might be second or third author on a Nature paper, but you’re not quite sure what they did. You get a lot of people like that. The supervisor would usually be someone I know, because they’re in my field. If the supervisor says ‘this is the best student I’ve ever seen’, you take that seriously…unless you’ve had six previous letters from that supervisor saying that same thing!”

“You’d also be looking at what skills they had. Sometimes you might get someone who’s very good at maths or statistics – that’s really good. Maths is always useful. Or they might have had a project with a lot of imaging in it, because it’s something we want to get into.

Our previous interviewee said that the programming was highly in demand, especially if combined with medicine. Do you agree?

“Yes. General IT skills are valuable. Medicine and programming is a valuable combination. I can see what that would be very good for him (our previous interviewee) and quite a few people here. I’d be pretty keen, though I wouldn’t say it’s essential for someone coming to my lab.”

Do you think there’s any skills shortages?

“It’s hard to say. New skill requirements come with new technologies. For instance, mass spectroscopy and proteomics. Probably 10 years ago nobody doing immunology knew what mass spectroscopy was. Now it’s widely used. To get it going, you need experts coming in from that field. They were all sitting down in the chemistry department. It’s the same with imaging now. With some of these super resolution imaging methods, we’re examining single molecules on cell surfaces, or within cells.”

Funding vs. talent constraints

For the good person who’s CV you just described, would you prefer their CV landing on your desk or an extra grant?

“It’s not a simple choice. If they’re that good, they’ll probably get their own funding at some point. You can take them on without huge risk. I would always take the person.”

How about if you could have half a million pound grant?

“It’s hard to turn down half a million pounds. I wouldn’t know many groups who would. You could buy another machine or do another project that would be too expensive otherwise. It depends on how much money I’ve got there already. It’s fantastic to get good people though, no question.”

Can good researchers always get funding?

“Yes, reasonably easily. Everyone can get bad patches. It’s unusual to always be on top of everything. For instance, you can get a dip at the end of a line of work, while you’re getting ready to start something else. But on the whole they can.”

Pandemics

Does anyone know the probability that a new flu strain turns into something really bad?

“We don’t really know, because we didn’t record most of the outbreaks before. Now we’re seeing transfer from birds into humans every couple of years. It’s mostly high mortality, but doesn’t transmit between humans.”

“If an infectious strain developed, it could cause a lot of damage. It would take 6 months to develop a vaccine.”

Has the time taken to produce a vaccine decreased?

“Yes, on the molecular biology end. We can go from a throat swab to a virus sequence in a matter of hours, then engineer into a vaccine in a week or two. In the past this took more like three months. But then you have to go through all the regulatory stuff, the manufacturing, this massive scale up. You’ve got to do some safety testing, because this is going to be given to millions of people. 6 months is what it takes.”

Could it be reduced even more?

“Just a couple of weeks. You really have to know that it generates the right antibody response, which in each individual takes 2-3 weeks per, and 2-3 months for a full study. For safety, you’ve got to give it to several thousand people to be sure there’s not a major problem.”

If you wanted to use your career to reduce the risk of pandemics, what should you do?

“You could go into vaccine research. Do your PhD in immunology, bioinformatics, microbiology, virology or background in public health. Virologists would say no vaccine has ever been developed by an immunologist, but there are a number of vaccine problems that definitely need immunology.

“You can also go into public health. In many countries HIV has been brought under control by public health, though you’ll never eradicate it without a vaccine. It’s also important for controlling flu outbreaks in the first 6 months. To take this route, do a diploma in public health. You don’t need to do a medical research. You can also enter from medical research. I’ve had lots of PhD students who’ve gone into public health.”

Job satisfaction and career progression

What’s the worst thing about this career?

“Overall, I think it’s a fantastic career. The downsides are that it’s not very secure. People can run into funding problems, especially if they’re not at the peak of things or a bit unlucky. It’s not particularly well paid. It has its ups and downs. The ups more than compensate, but when you have a string of bad results and grants rejected, it gets a bit depressing.”

“It can leave people a bit stranded mid career. You start out well, but you don’t quite make it to the top. You’re on a 3-5 year contract. You find it doesn’t get renewed. You’re 45 and stranded.

What happens then?

“You can take jobs in lab admin, lab managers, research councils. It’s better to go into these careers at the start, but it’s an option. It’s difficult to go into medicine by this stage. People have, but it’s not ideal. Others just leave science, and go on to do other worthwhile things. One guy I know who went and started a coffee chain and did really well!”

How can someone early in their career evaluate their prospects?

“This career is hard to predict. You have someone just starting their PhD. It’s quite hard to predict how it’s going to go for them. If they’ve done really well, they’ll probably succeed, but probably not quite as they imagine. And you may find that, although you’re first author on a Nature paper, you relied on having a great mentor. If they haven’t done really well, they can succeed, I’ve seen it happen. More likely, they’ll have to do something else.”

“You’ll need to bear in mind that if it’s not working out, you may need to think about alternatives. It’s better to make the decision at that point rather than in 10 years. You can help yourself a lot by going to a top lab. Then ask, are you swimming or sinking?”